Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders

Kenneth       Maiese
Abstract

Neurodegenerative disorders impact more than one billion individuals worldwide and are intimately tied to metabolic disease that can affect another nine hundred individuals throughout the globe. Nicotinamide is a critical agent that may offer fruitful prospects for neurodegenerative diseases and metabolic disorders, such as diabetes mellitus. Nicotinamide protects against multiple toxic environments that include reactive oxygen species exposure, anoxia, excitotoxicity, ethanolinduced neuronal injury, amyloid (Aß) toxicity, age-related vascular disease, mitochondrial dysfunction, insulin resistance, excess lactate production, and loss of glucose homeostasis with pancreatic β-cell dysfunction. However, nicotinamide offers cellular protection in a specific concentration range, with dosing outside of this range leading to detrimental effects. The underlying biological pathways of nicotinamide that involve the silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), and mammalian forkhead transcription factors (FoxOs) may offer insight for the clinical translation of nicotinamide into a safe and efficacious therapy through the modulation of oxidative stress, apoptosis, and autophagy. Nicotinamide is a highly promising target for the development of innovative strategies for neurodegenerative disorders and metabolic disease, but the benefits of this foundation depend greatly on gaining a further understanding of nicotinamide’s complex biology.
Keywords: Alzheimer's disease, AMP activated protein kinase (AMPK), autophagy, apoptosis, dementia, diabetes mellitus, forkhead transcription factors, FoxO, mechanistic target of rapamycin (mTOR), oxidative stress, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae) (SIRT1), sirtuin, stem cells.
« Previous Next »
[1] 
Maiese K, Chong ZZ, Hou J, Shang YC. The vitamin nicotinamide: Translating nutrition into clinical care. Molecules  2009; 14(9): 3446-85.
[http://dx.doi.org/10.3390/molecules14093446] [PMID: 19783937] 
[2] 
Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. Exp Gerontol  2020; 132: 110831.
[http://dx.doi.org/10.1016/j.exger.2020.110831] [PMID: 31917996] 
[3] 
Rex A, Fink H. Pharmacokinetic aspects of reduced nicotinamide adenine dinucleotide (NADH) in rats. Front Biosci  2008; 13: 3735-41.
[http://dx.doi.org/10.2741/2962] [PMID: 18508468] 
[4] 
Li F, Chong ZZ, Maiese K. Navigating novel mechanisms of cellular plasticity with the NAD+ precursor and nutrient nicotinamide. Front Biosci  2004; 9: 2500-20.
[http://dx.doi.org/10.2741/1412] [PMID: 15353303] 
[5] 
Maiese K, Chong ZZ. Nicotinamide: Necessary nutrient emerges as a novel cytoprotectant for the brain. Trends Pharmacol Sci  2003; 24(5): 228-32.
[http://dx.doi.org/10.1016/S0165-6147(03)00078-6] [PMID: 12767721] 
[6] 
Jackson TM, Rawling JM, Roebuck BD, Kirkland JB. Large supplements of nicotinic acid and nicotinamide increase tissue NAD+ and poly(ADP-ribose) levels but do not affect diethylnitrosamine-induced altered hepatic foci in Fischer-344 rats. J Nutr  1995; 125(6): 1455-61.
[PMID: 7782898] 
[7] 
Wojcik M, Seidle HF, Bieganowski P, Brenner C. Glutamine-dependent NAD+ synthetase. How a two-domain, three-substrate enzyme avoids waste. J Biol Chem  2006; 281(44): 33395-402.
[http://dx.doi.org/10.1074/jbc.M607111200] [PMID: 16954203] 
[8] 
Khan JA, Forouhar F, Tao X, Tong L. Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery. Expert Opin Ther Targets  2007; 11(5): 695-705.
[http://dx.doi.org/10.1517/14728222.11.5.695] [PMID: 17465726] 
[9] 
Khan JA, Xiang S, Tong L. Crystal structure of human nicotinamide riboside kinase. Structure  2007; 15(8): 1005-13.
[http://dx.doi.org/10.1016/j.str.2007.06.017] [PMID: 17698003] 
[10] 
Li F, Chong ZZ, Maiese K. Cell Life versus cell longevity: The mysteries surrounding the NAD+ precursor nicotinamide. Curr Med Chem  2006; 13(8): 883-95.
[http://dx.doi.org/10.2174/092986706776361058] [PMID: 16611073] 
[11] 
Maiese K. Triple play: promoting neurovascular longevity with nicotinamide, WNT, and erythropoietin in diabetes mellitus. Biomed Pharmacother  2008; 62(4): 218-32.
[http://dx.doi.org/10.1016/j.biopha.2008.01.009] [PMID: 18342481] 
[12] 
Maiese K. New Insights for nicotinamide: Metabolic disease, autophagy, and mTOR. Front Biosci  2020; 25: 1925-73.
[http://dx.doi.org/10.2741/4886] [PMID: 32472766] 
[13] 
Magni G, Amici A, Emanuelli M, Orsomando G, Raffaelli N, Ruggieri S. Enzymology of NAD+ homeostasis in man. Cell Mol Life Sci  2004; 61(1): 19-34.
[http://dx.doi.org/10.1007/s00018-003-3161-1] [PMID: 14704851] 
[14] 
Lin SJ, Guarente L. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr Opin Cell Biol  2003; 15(2): 241-6.
[http://dx.doi.org/10.1016/S0955-0674(03)00006-1] [PMID: 12648681] 
[15] 
Hageman GJ, Stierum RH. Niacin, poly(ADP-ribose) polymerase-1 and genomic stability. Mutat Res  2001; 475(1-2): 45-56.
[http://dx.doi.org/10.1016/S0027-5107(01)00078-1] [PMID: 11295153] 
[16] 
Castro-Portuguez R, Sutphin GL. Kynurenine pathway, NAD+ synthesis, and mitochondrial function: Targeting tryptophan metabolism to promote longevity and healthspan. Exp Gerontol  2020; 132: 110841.
[http://dx.doi.org/10.1016/j.exger.2020.110841] [PMID: 31954874] 
[17] 
Feng Y, Wang Y, Jiang C, et al. Nicotinamide induces mitochondrial-mediated apoptosis through oxidative stress in human cervical cancer HeLa cells. Life Sci  2017; 181: 62-9.
[http://dx.doi.org/10.1016/j.lfs.2017.06.003] [PMID: 28591568] 
[18] 
Maiese K. The bright side of reactive oxygen species: Lifespan extension without cellular demise. J Transl Sci  2016; 2(3): 185-7.
[http://dx.doi.org/10.15761/JTS.1000138] [PMID: 27200181] 
[19] 
Poljsak B, Milisav I. NAD(+) as the link between oxidative stress, inflammation, caloric restriction, exercise, DNA repair, longevity and health span. Rejuvenation Res  2016; 19(5): 406-15.
[http://dx.doi.org/10.1089/rej.2015.1767] [PMID: 26725653] 
[20] 
Csiszar A, Tarantini S, Yabluchanskiy A, et al. Role of endothelial NAD+ deficiency in age-related vascular dysfunction. Am J Physiol Heart Circ Physiol  2019; 316(6): H1253-66.
[http://dx.doi.org/10.1152/ajpheart.00039.2019] [PMID: 30875255] 
[21] 
Williams AC, Hill LJ, Ramsden DB. Nicotinamide, NAD(P)(H), and methyl-group homeostasis evolved and became a determinant of ageing diseases: Hypotheses and lessons from pellagra. Curr Gerontol Geriatr Res  2012; 2012: 302875.
[http://dx.doi.org/10.1155/2012/302875] [PMID: 22536229] 
[22] 
Ieraci A, Herrera DG. Nicotinamide protects against ethanol-induced apoptotic neurodegeneration in the developing mouse brain. PLoS Med  2006; 3(4): e101.
[http://dx.doi.org/10.1371/journal.pmed.0030101] [PMID: 16478293] 
[23] 
Ieraci A, Herrera DG. Nicotinamide inhibits ethanol-induced Caspase-3 and PARP-1 over-activation and subsequent neurodegeneration in the developing mouse cerebellum. Cerebellum (London, England)  2018; 17(3): 326-35.https://pubmed.ncbi.nlm.nih.gov/29327278/
[24] 
Maiese K. Nicotinamide: Oversight of metabolic dysfunction through SIRT1, mTOR, and clock genes. Curr Neurovasc Res  2020; 17(5): 765-83.https://pubmed.ncbi.nlm.nih.gov/33183203/
[PMID: 33183203] 
[25] 
Maiese K, Chong ZZ, Hou J, Shang YC. Oxidative stress: Biomarkers and novel therapeutic pathways. Exp Gerontol  2010; 45(3): 217-34.
[http://dx.doi.org/10.1016/j.exger.2010.01.004] [PMID: 20064603] 
[26] 
Maiese K. New insights for oxidative stress and diabetes mellitus. Oxid Med Cell Longev  2015; 2015: 875961.
[http://dx.doi.org/10.1155/2015/875961] 
[27] 
Stefano GB, Kream RM. Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective (Review). Int J Mol Med  2016; 37(3): 547-55.
[http://dx.doi.org/10.3892/ijmm.2016.2471] [PMID: 26821064] 
[28] 
Tafani M, Sansone L, Limana F, et al. The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression. Oxid Med Cell Longev  2016; 2016: 3907147.
[http://dx.doi.org/10.1155/2016/3907147] [PMID: 26798421] 
[29] 
Maiese K. Molecules to medicine with mTOR: Translating critical pathways into novel therapeutic strategies. Academic Press, Elsevier 2016.
[30] 
Maiese K. Prospects and perspectives for WISP1 (CCN4) in diabetes mellitus. Curr Neurovasc Res  2020; 17(3): 327-31.
[http://dx.doi.org/10.2174/1567202617666200327125257] [PMID: 32216738] 
[31] 
Doroftei B, Ilie OD, Cojocariu RO, et al. Mini-review exploring the biological cycle of vitamin b3 and its influence on oxidative stress: Further molecular and clinical aspects. Molecules  2020; 25(15): 3323.
[http://dx.doi.org/10.3390/molecules25153323] [PMID: 32707945] 
[32] 
Li X, Feng Y, Wang XX, Truong D, Wu YC. The critical role of SIRT1 in Parkinson’s disease: Mechanism and therapeutic considerations. Aging Dis  2020; 11(6): 1608-22.
[http://dx.doi.org/10.14336/AD.2020.0216] [PMID: 33269110] 
[33] 
Mladenovic Djordjevic A, Loncarevic-Vasiljkovic N, Gonos ES. Dietary restriction and oxidative stress: Friends or enemies? Antioxid Redox Signal  2020; 2020: 7959.
[http://dx.doi.org/10.1089/ars.2019.7959] [PMID: 32242468] 
[34] 
Mocayar Marón FJ, Ferder L, Reiter RJ, Manucha W. Daily and seasonal mitochondrial protection: Unraveling common possible mechanisms involving vitamin D and melatonin. J Steroid Biochem Mol Biol  2020; 199: 105595.
[http://dx.doi.org/10.1016/j.jsbmb.2020.105595] [PMID: 31954766] 
[35] 
Wu L, Xiong X, Wu X, et al. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci  2020; 13: 28.
[http://dx.doi.org/10.3389/fnmol.2020.00028] [PMID: 32194375] 
[36] 
Zhao HY, Li HY, Jin J, et al. L-carnitine treatment attenuates renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. Korean J Intern Med (Korean Assoc Intern Med)  2020; 2020: 413.
[http://dx.doi.org/10.3904/kjim.2019.413] [PMID: 32942841] 
[37] 
Scialò F, Sriram A, Fernández-Ayala D, et al. Mitochondrial ROS produced via reverse electron transport extend animal lifespan. Cell Metab  2016; 23(4): 725-34.
[http://dx.doi.org/10.1016/j.cmet.2016.03.009] [PMID: 27076081] 
[38] 
Lawler JM, Rodriguez DA, Hord JM. Mitochondria in the middle: Exercise preconditioning protection of striated muscle. J Physiol  2016; 594(18): 5161-83.
[http://dx.doi.org/10.1113/JP270656] [PMID: 27060608] 
[39] 
You H, Li T, Zhang J, et al. Reduction in ischemic cerebral infarction is mediated through golgi phosphoprotein 3 and Akt/mTOR signaling following salvianolate administration. Curr Neurovasc Res  2014; 11(2): 107-13.
[http://dx.doi.org/10.2174/1567202611666140307124857] [PMID: 24606552] 
[40] 
Zhou Y, Fang H, Lin S, et al. Qiliqiangxin protects against cardiac ischemia-reperfusion injury via activation of the mTOR pathway. Cell Physiol Biochem  2015; 37(2): 454-64.
[http://dx.doi.org/10.1159/000430368] [PMID: 26315320] 
[41] 
Maiese K. Cognitive impairment with diabetes mellitus and metabolic disease: Innovative insights with the mechanistic target of rapamycin and circadian clock gene pathways. Expert Rev Clin Pharmacol  2020; 13(1): 23-34.
[http://dx.doi.org/10.1080/17512433.2020.1698288] [PMID: 31794280] 
[42] 
Dai C, Xiao X, Zhang Y, et al. Curcumin attenuates colistin-induced peripheral neurotoxicity in mice. ACS Infect Dis  2020; 6(4): 715-24.
[http://dx.doi.org/10.1021/acsinfecdis.9b00341] [PMID: 32037797] 
[43] 
Deng D, Yan J, Wu Y, Wu K, Li W. Morroniside suppresses hydrogen peroxide-stimulated autophagy and apoptosis in rat ovarian granulosa cells through the PI3K/AKT/mTOR pathway. Hum Exp Toxicol  2020; 40(4): 77-586.
[http://dx.doi.org/10.1177/0960327120960768] [PMID: 32954801] 
[44] 
Jayaraj RL, Beiram R, Azimullah S, et al. Valeric acid protects dopaminergic neurons by suppressing oxidative stress, neuroinflammation and modulating autophagy pathways. Int J Mol Sci  2020; 21(20): E7670.
[http://dx.doi.org/10.3390/ijms21207670] [PMID: 33081327] 
[45] 
Meng J, Chen Y, Wang J, et al. EGCG protects vascular endothelial cells from oxidative stress-induced damage by targeting the autophagy-dependent PI3K-AKT-mTOR pathway. Ann Transl Med  2020; 8(5): 200.
[http://dx.doi.org/10.21037/atm.2020.01.92] [PMID: 32309347] 
[46] 
Yang J, Suo H, Song J. Protective role of mitoquinone against impaired mitochondrial homeostasis in metabolic syndrome. Crit Rev Food Sci Nutr  2020; 20: 1-19.
[PMID: 32815398] 
[47] 
Liu JD, Deng Q, Tian HH, Pang YT, Deng GL. Wnt/glycogen synthase kinase 3β/β-catenin signaling activation mediated sevoflurane preconditioning-induced cardioprotection. Chin Med J (Engl)  2015; 128(17): 2346-53.
[http://dx.doi.org/10.4103/0366-6999.163375] [PMID: 26315083] 
[48] 
Maiese K. Novel applications of trophic factors, Wnt and WISP for neuronal repair and regeneration in metabolic disease. Neural Regen Res  2015; 10(4): 518-28.
[http://dx.doi.org/10.4103/1673-5374.155427] [PMID: 26170801] 
[49] 
Maiese K, Li F, Chong ZZ, Shang YC. The Wnt signaling pathway: Aging gracefully as a protectionist? Pharmacol Ther  2008; 118(1): 58-81.
[http://dx.doi.org/10.1016/j.pharmthera.2008.01.004] [PMID: 18313758] 
[50] 
Jarero-Basulto JJ, Rivera-Cervantes MC, Gasca-Martínez D, García-Sierra F, Gasca-Martínez Y, Beas-Zárate C. Current evidence on the protective effects of recombinant human erythropoietin and its molecular variants against pathological hallmarks of alzheimer’s disease. Pharmaceuticals (Basel)  2020; 13(12): 1-22.
[http://dx.doi.org/10.3390/ph13120424] [PMID: 33255969] 
[51] 
Li N, Yue L, Wang J, Wan Z, Bu W. MicroRNA-24 alleviates isoflurane-induced neurotoxicity in rat hippocampus via attenuation of oxidative stress. Biochem Cell Biol  2020; 98(2): 208-18.
[http://dx.doi.org/10.1139/bcb-2019-0188] [PMID: 31533001] 
[52] 
Maiese K. The mechanistic target of rapamycin (mTOR): Novel considerations as an antiviral treatment. Curr Neurovasc Res  2020; 17(3): 332-7.
[http://dx.doi.org/10.2174/1567202617666200425205122] [PMID: 32334502] 
[53] 
Speer H, D’Cunha NM, Alexopoulos NI, McKune AJ, Naumovski N. Anthocyanins and human health-a focus on oxidative stress, inflammation and disease. Antioxidants  2020; 9(5): 366.
[http://dx.doi.org/10.3390/antiox9050366] [PMID: 32353990] 
[54] 
Xie T, Ye W, Liu J, Zhou L, Song Y. The Emerging Key Role of Klotho in the Hypothalamus-Pituitary-Ovarian Axis. Reprod Sci  2021; 28: 322-31.
[http://dx.doi.org/10.1007/s43032-020-00277-5] [PMID: 32783104] 
[55] 
Balan V, Miller GS, Kaplun L, et al. Life span extension and neuronal cell protection by Drosophila nicotinamidase. J Biol Chem  2008; 283(41): 27810-9.
[http://dx.doi.org/10.1074/jbc.M804681200] [PMID: 18678867] 
[56] 
Lai YF, Wang L, Liu WY. Nicotinamide pretreatment alleviates mitochondrial stress and protects hypoxic myocardial cells via AMPK pathway. Eur Rev Med Pharmacol Sci  2019; 23(4): 1797-806.
[PMID: 30840306] 
[57] 
Maiese K, Chong ZZ, Shang YC, Hou J. Novel avenues of drug discovery and biomarkers for diabetes mellitus. J Clin Pharmacol  2011; 51(2): 128-52.
[http://dx.doi.org/10.1177/0091270010362904] [PMID: 20220043] 
[58] 
Perez-Lobos R, Lespay-Rebolledo C, Tapia-Bustos A, et al. Vulnerability to a metabolic challenge following perinatal asphyxia evaluated by organotypic cultures: Neonatal nicotinamide treatment. Neurotox Res  2017; 32(3): 426-43.https://pubmed.ncbi.nlm.nih.gov/28631256/
[59] 
Mahmoud YI, Mahmoud AA. Role of nicotinamide (vitamin B3) in acetaminophen-induced changes in rat liver: Nicotinamide effect in acetaminophen-damged liver. Exp Toxicol Pathol  2016; 68(6): 345-54.
[http://dx.doi.org/10.1016/j.etp.2016.05.003] [PMID: 27211843] 
[60] 
Marshall CA, Borbon IA, Erickson RP. Relative efficacy of nicotinamide treatment of a mouse model of infantile Niemann-Pick C1 disease. J Appl Genet  2017; 58(1): 99-102.
[PMID: 27783333] 
[61] 
Chong ZZ, Lin SH, Maiese K. The NAD+ precursor nicotinamide governs neuronal survival during oxidative stress through protein kinase B coupled to FOXO3a and mitochondrial membrane potential. J Cereb Blood Flow Metab  2004; 24(7): 728-43.
[http://dx.doi.org/10.1097/01.WCB.0000122746.72175.0E] [PMID: 15241181] 
[62] 
Chong ZZ, Maiese K. Enhanced tolerance against early and late apoptotic oxidative stress in mammalian neurons through nicotinamidase and sirtuin mediated pathways. Curr Neurovasc Res  2008; 5(3): 159-70.
[http://dx.doi.org/10.2174/156720208785425666] [PMID: 18691073] 
[63] 
Maiese K. mTOR: Driving apoptosis and autophagy for neurocardiac complications of diabetes mellitus. World J Diabetes  2015; 6(2): 217-24.
[http://dx.doi.org/10.4239/wjd.v6.i2.217] [PMID: 25789103] 
[64] 
Mikhed Y, Daiber A, Steven S. Mitochondrial oxidative stress, mitochondrial dna damage and their role in age-related vascular dysfunction. Int J Mol Sci  2015; 16(7): 15918-53.
[http://dx.doi.org/10.3390/ijms160715918] [PMID: 26184181] 
[65] 
Parmar MS, Syed I, Gray JP, Ray SD. Curcumin, Hesperidin, and Rutin selectively interfere with apoptosis signaling and attenuate streptozotocin-induced oxidative stress-mediated hyperglycemia. Curr Neurovasc Res  2015; 12(4): 363-74.
[http://dx.doi.org/10.2174/1567202612666150812150249] [PMID: 26265154] 
[66] 
Pérez-Gallardo RV, Noriega-Cisneros R, Esquivel-Gutiérrez E, et al. Effects of diabetes on oxidative and nitrosative stress in kidney mitochondria from aged rats. J Bioenerg Biomembr  2014; 46(6): 511-8.
[http://dx.doi.org/10.1007/s10863-014-9594-4] [PMID: 25425473] 
[67] 
Wang P, Xing Y, Chen C, Chen Z, Qian Z. Advanced glycation end-product (AGE) induces apoptosis in human retinal ARPE-19 cells via promoting mitochondrial dysfunction and activating the Fas-FasL signaling. Biosci Biotechnol Biochem  2016; 80(2): 250-6.
[http://dx.doi.org/10.1080/09168451.2015.1095065] [PMID: 26479732] 
[68] 
Maiese K. The mechanistic target of rapamycin (mTOR) and the silent mating-type information regulation 2 homolog 1 (SIRT1): Oversight for neurodegenerative disorders. Biochem Soc Trans  2018; 46(2): 351-60.
[http://dx.doi.org/10.1042/BST20170121] [PMID: 29523769] 
[69] 
Maiese K. Targeting the core of neurodegeneration: FoxO, mTOR, and SIRT1. Neural Regen Res  2021; 16(3): 448-55.
[http://dx.doi.org/10.4103/1673-5374.291382] [PMID: 32985464] 
[70] 
Hou J, Chong ZZ, Shang YC, Maiese K. Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation. Curr Neurovasc Res  2010; 7(2): 95-112.
[http://dx.doi.org/10.2174/156720210791184899] [PMID: 20370652] 
[71] 
Shang YC, Chong ZZ, Hou J, Maiese K. Wnt1, FoxO3a, and NF-kappaB oversee microglial integrity and activation during oxidant stress. Cell Signal  2010; 22(9): 1317-29.
[http://dx.doi.org/10.1016/j.cellsig.2010.04.009] [PMID: 20462515] 
[72] 
Taveira GB, Mello EO, Souza SB, et al. Programmed cell death in yeast by thionin-like peptide from Capsicum annuum fruits involving activation of caspases and extracellular H+ flux. Biosci Rep  2018; 38(2): BSR20180119.
[http://dx.doi.org/10.1042/BSR20180119] [PMID: 29599127] 
[73] 
Hou J, Wang S, Shang YC, Chong ZZ, Maiese K. Erythropoietin employs cell longevity pathways of SIRT1 to foster endothelial vascular integrity during oxidant stress. Curr Neurovasc Res  2011; 8(3): 220-35.
[http://dx.doi.org/10.2174/156720211796558069] [PMID: 21722091] 
[74] 
Bhowmick S, D'Mello V, Caruso D, Abdul-Muneer PM. Traumatic brain injury-induced downregulation of Nrf2 activates inflammatory response and apoptotic cell death. J Mol Med  2019; 97(12): 1627-41.
[http://dx.doi.org/10.1007/s00109-019-01851-4] 
[75] 
Finelli MJ, Liu KX, Wu Y, Oliver PL, Davies KE. Oxr1 improves pathogenic cellular features of ALS-associated FUS and TDP-43 mutations. Hum Mol Genet  2015; 24(12): 3529-44.
[http://dx.doi.org/10.1093/hmg/ddv104] [PMID: 25792726] 
[76] 
Maiese K. Programming apoptosis and autophagy with novel approaches for diabetes mellitus. Curr Neurovasc Res  2015; 12(2): 173-88.
[http://dx.doi.org/10.2174/1567202612666150305110929] [PMID: 25742566] 
[77] 
Millet A, Bouzat P, Trouve-Buisson T, et al. Erythropoietin and its derivates modulate mitochondrial dysfunction after diffuse traumatic brain injury. J Neurotrauma  2016; 33(17): 1625-33.
[http://dx.doi.org/10.1089/neu.2015.4160] [PMID: 26530102] 
[78] 
Hou J, Chong ZZ, Shang YC, Maiese K. FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling. Mol Cell Endocrinol  2010; 321(2): 194-206.
[http://dx.doi.org/10.1016/j.mce.2010.02.037] [PMID: 20211690] 
[79] 
Maiese K. Targeting molecules to medicine with mTOR, autophagy and neurodegenerative disorders. Br J Clin Pharmacol  2016; 82(5): 1245-66.
[http://dx.doi.org/10.1111/bcp.12804] [PMID: 26469771] 
[80] 
Saleem S, Biswas SC. Tribbles Pseudokinase 3 induces both apoptosis and autophagy in Amyloid-β-induced neuronal death. J Biol Chem  2017; 292(7): 2571-85.
[http://dx.doi.org/10.1074/jbc.M116.744730] [PMID: 28011637] 
[81] 
Ullah R, Khan M, Shah SA, Saeed K, Kim MO. Natural Antioxidant Anthocyanins-A hidden therapeutic candidate in metabolic disorders with major focus in neurodegeneration. Nutrients  2019; 11(6): E1195.
[http://dx.doi.org/10.3390/nu11061195] [PMID: 31141884] 
[82] 
Liang CJ, Li JH, Zhang Z, Zhang JY, Liu SQ, Yang J. Suppression of MIF-induced neuronal apoptosis may underlie the therapeutic effects of effective components of Fufang Danshen in the treatment of Alzheimer’s disease. Acta Pharmacol Sin  2018; 39(9): 1421-38.
[http://dx.doi.org/10.1038/aps.2017.210] [PMID: 29770796] 
[83] 
El-Missiry MA, Othman AI, Amer MA, Sedki M, Ali SM, El-Sherbiny IM. Nanoformulated ellagic acid ameliorates pentylenetetrazol-induced experimental epileptic seizures by modulating oxidative stress, inflammatory cytokines and apoptosis in the brains of male mice. Metab Brain Dis  2020; 35(2): 385-99.https://pubmed.ncbi.nlm.nih.gov/31728888/
[PMID: 31728888] 
[84] 
Yue J, Liang C, Wu K, et al. Upregulated SHP-2 expression in the epileptogenic zone of temporal lobe epilepsy and various effects of SHP099 treatment on a pilocarpine model. Brain Pathol  2019; 30(2): 373-85.https://pubmed.ncbi.nlm.nih.gov/31398269/
[PMID: 31398269] 
[85] 
Almasieh M, Catrinescu MM, Binan L, Costantino S, Levin LA. Axonal degeneration in retinal ganglion cells is associated with a membrane polarity-sensitive redox process. J Neurosci  2017; 37(14): 3824-39.
[http://dx.doi.org/10.1523/JNEUROSCI.3882-16.2017] [PMID: 28275163] 
[86] 
Tao Y, Li C, Yao A, et al. Intranasal administration of erythropoietin rescues the photoreceptors in degenerative retina: A noninvasive method to deliver drugs to the eye. Drug Deliv  2019; 26(1): 78-88.
[http://dx.doi.org/10.1080/10717544.2018.1556361] [PMID: 30744451] 
[87] 
Zhao Y, Wang Q, Wang Y, Li J, Lu G, Liu Z. Glutamine protects against oxidative stress injury through inhibiting the activation of PI3K/Akt signaling pathway in parkinsonian cell model. Environ Health Prev Med  2019; 24(1): 4.
[http://dx.doi.org/10.1186/s12199-018-0757-5] [PMID: 30611190] 
[88] 
Dehghanian F, Soltani Z, Khaksari M. Can mesenchymal stem cells act multipotential in traumatic brain injury? J Mol Neurosci  2020; 70(5): 677-88.
[http://dx.doi.org/10.1007/s12031-019-01475-w] [PMID: 31897971] 
[89] 
Sun F, Li SG, Zhang HW, Hua FW, Sun GZ, Huang Z. MiRNA-411 attenuates inflammatory damage and apoptosis following spinal cord injury. Eur Rev Med Pharmacol Sci  2020; 24(2): 491-8.
[PMID: 32016950] 
[90] 
Wang Z, Qiu Z, Gao C, et al. 2,5-hexanedione downregulates nerve growth factor and induces neuron apoptosis in the spinal cord of rats via inhibition of the PI3K/Akt signaling pathway. PLoS One  2017; 12(6): e0179388.
[http://dx.doi.org/10.1371/journal.pone.0179388] [PMID: 28654704] 
[91] 
Xu D, Li F, Hou K, Gou X, Fang W, Li Y. XQ-1H attenuates ischemic injury in PC12 cells via Wnt/β-catenin signaling though inhibition of apoptosis and promotion of proliferation. Cell Biol Int  2020; 44(11): 2363-9.
[http://dx.doi.org/10.1002/cbin.11438] [PMID: 32761926] 
[92] 
Zhao C, Li W, Duan H, et al. NAD+ precursors protect corneal endothelial cells from UVB-induced apoptosis. Am J Physiol Cell Physiol  2020; 318(4): C796-805.
[http://dx.doi.org/10.1152/ajpcell.00445.2019] [PMID: 32049549] 
[93] 
Zhou Q, Zhou S, Wang H, Li Y, Xiao X, Yang J. Stable silencing of ROR1 regulates cell cycle, apoptosis, and autophagy in a lung adenocarcinoma cell line. Int J Clin Exp Pathol  2020; 13(5): 1108-20.
[PMID: 32509086] 
[94] 
Simon F, Floros N, Ibing W, Schelzig H, Knapsis A. Neurotherapeutic potential of erythropoietin after ischemic injury of the central nervous system. Neural Regen Res  2019; 14(8): 1309-12.
[http://dx.doi.org/10.4103/1673-5374.253507] [PMID: 30964047] 
[95] 
Wang W, Han P, Xie R, et al. TAT-mGluR1 Attenuates Neuronal Apoptosis Through Preventing MGluR1alpha Truncation after Experimental Subarachnoid Hemorrhage. ACS Chem Neurosci  2019; 10(1): 746-56.
[96] 
Maiese K, Vincent AM. Membrane asymmetry and DNA degradation: functionally distinct determinants of neuronal programmed cell death. J Neurosci Res  2000; 59(4): 568-80.
[http://dx.doi.org/10.1002/(SICI)1097-4547(20000215)59:4<568::AID-JNR13>3.0.CO;2-R] [PMID: 10679797] 
[97] 
Schutters K, Reutelingsperger C. Phosphatidylserine targeting for diagnosis and treatment of human diseases. Apoptosis  2010; 15(9): 1072-82.
[http://dx.doi.org/10.1007/s10495-010-0503-y] [PMID: 20440562] 
[98] 
Wei L, Sun C, Lei M, et al. Activation of Wnt/β-catenin pathway by exogenous Wnt1 protects SH-SY5Y cells against 6-hydroxydopamine toxicity. J Mol Neurosci  2013; 49(1): 105-15.
[http://dx.doi.org/10.1007/s12031-012-9900-8] [PMID: 23065334] 
[99] 
Williams CJ, Dexter DT. Neuroprotective and symptomatic effects of targeting group III mGlu receptors in neurodegenerative disease. J Neurochem  2014; 129(1): 4-20.
[http://dx.doi.org/10.1111/jnc.12608] [PMID: 24224472] 
[100] 
Chong ZZ, Lin SH, Li F, Maiese K. The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated “anti-apoptotic” pathways. Curr Neurovasc Res  2005; 2(4): 271-85.
[http://dx.doi.org/10.2174/156720205774322584] [PMID: 16181120] 
[101] 
Chong ZZ, Lin SH, Maiese K. Nicotinamide modulates mitochondrial membrane potential and cysteine protease activity during cerebral vascular endothelial cell injury. J Vasc Res  2002; 39(2): 131-47.
[http://dx.doi.org/10.1159/000057762] [PMID: 12011585] 
[102] 
Lin SH, Vincent A, Shaw T, Maynard KI, Maiese K. Prevention of nitric oxide-induced neuronal injury through the modulation of independent pathways of programmed cell death. J Cereb Blood Flow Metab  2000; 20(9): 1380-91.
[http://dx.doi.org/10.1097/00004647-200009000-00013] [PMID: 10994860] 
[103] 
Bombeli T, Karsan A, Tait JF, Harlan JM. Apoptotic vascular endothelial cells become procoagulant. Blood  1997; 89(7): 2429-42.
[http://dx.doi.org/10.1182/blood.V89.7.2429] [PMID: 9116287] 
[104] 
Chong ZZ, Kang JQ, Maiese K. Angiogenesis and plasticity: Role of erythropoietin in vascular systems. J Hematother Stem Cell Res  2002; 11(6): 863-71.
[http://dx.doi.org/10.1089/152581602321080529] [PMID: 12590701] 
[105] 
Maiese K, Chong ZZ, Shang YC. Raves and risks for erythropoietin. Cytokine Growth Factor Rev  2008; 19(2): 145-55.
[http://dx.doi.org/10.1016/j.cytogfr.2008.01.004] [PMID: 18299246] 
[106] 
Lin SH, Chong ZZ, Maiese K. Nicotinamide: A nutritional supplement that provides protection against neuronal and vascular injury. J Med Food  2001; 4(1): 27-38.
[http://dx.doi.org/10.1089/10966200152053686] [PMID: 12639285] 
[107] 
Jackson MD, Schmidt MT, Oppenheimer NJ, Denu JM. Mechanism of nicotinamide inhibition and transglycosidation by Sir2 histone/protein deacetylases. J Biol Chem  2003; 278(51): 50985-98.
[http://dx.doi.org/10.1074/jbc.M306552200] [PMID: 14522996] 
[108] 
Kruszewski M, Szumiel I. Sirtuins (histone deacetylases III) in the cellular response to DNA damage--facts and hypotheses. DNA Repair (Amst)  2005; 4(11): 1306-13.
[http://dx.doi.org/10.1016/j.dnarep.2005.06.013] [PMID: 16084131] 
[109] 
Ali T, Rahman SU, Hao Q, et al. Melatonin prevents neuroinflammation and relieves depression by attenuating autophagy impairment through FOXO3a regulation. J Pineal Res  2020; 69(2): e12667.
[http://dx.doi.org/10.1111/jpi.12667] [PMID: 32375205] 
[110] 
Boga JA, Coto-Montes A. ER stress and autophagy induced by SARS-CoV-2: The targets for melatonin treatment. Melatonin Research  2020; 3(3): 346-61.
[http://dx.doi.org/10.32794/mr11250067] 
[111] 
Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy  2016; 12(1): 1-222.
[112] 
Maiese K, Chong ZZ, Shang YC, Wang S. Targeting disease through novel pathways of apoptosis and autophagy. Expert Opin Ther Targets  2012; 16(12): 1203-14.
[http://dx.doi.org/10.1517/14728222.2012.719499] [PMID: 22924465] 
[113] 
Qi X, Mitter SK, Yan Y, Busik JV, Grant MB, Boulton ME. Diurnal rhythmicity of autophagy is impaired in the diabetic retina. Cells  2020; 9(4): 905.
[http://dx.doi.org/10.3390/cells9040905] [PMID: 32272782] 
[114] 
Wong SQ, Kumar AV, Mills J, Lapierre LR. C. elegans to model autophagy-related human disorders. Prog Mol Biol Transl Sci  2020; 172: 325-73.
[http://dx.doi.org/10.1016/bs.pmbts.2020.01.007] [PMID: 32620247] 
[115] 
Martino L, Masini M, Novelli M, et al. Palmitate activates autophagy in INS-1E β-cells and in isolated rat and human pancreatic islets. PLoS One  2012; 7(5): e36188.
[http://dx.doi.org/10.1371/journal.pone.0036188] [PMID: 22563482] 
[116] 
Liu Z, Stanojevic V, Brindamour LJ, Habener JF. GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β-cells from glucolipotoxicity. J Endocrinol  2012; 213(2): 143-54.
[http://dx.doi.org/10.1530/JOE-11-0328] [PMID: 22414687] 
[117] 
Dorvash M, Farahmandnia M, Tavassoly I. A systems biology roadmap to decode mTOR control system in cancer. Interdiscip Sci  2020; 12(1): 1-11.
[http://dx.doi.org/10.1007/s12539-019-00347-6] [PMID: 31531812] 
[118] 
Preau S, Ambler M, Sigurta A, et al. Protein recycling and limb muscle recovery after critical illness in slow- and fast-twitch limb muscle. Am J Physiol Regul Integr Comp Physiol  2019; 316(5): R584-93.
[http://dx.doi.org/10.1152/ajpregu.00221.2018] [PMID: 30789789] 
[119] 
Corti O, Blomgren K, Poletti A, Beart PM. Autophagy in neurodegeneration: New insights underpinning therapy for neurological diseases. J Neurochem  2020; 154(4): 354-71.
[http://dx.doi.org/10.1111/jnc.15002] [PMID: 32149395] 
[120] 
Fields CR, Bengoa-Vergniory N, Wade-Martins R. Targeting alpha-synuclein as a therapy for parkinson’s disease. Front Mol Neurosci  2019; 12: 299.
[http://dx.doi.org/10.3389/fnmol.2019.00299] [PMID: 31866823] 
[121] 
Tatullo M, Marrelli B, Zullo MJ, et al. Exosomes from human periapical cyst-MSCs: Theranostic application in parkinson’s disease. Int J Med Sci  2020; 17(5): 657-63.
[http://dx.doi.org/10.7150/ijms.41515] [PMID: 32210716] 
[122] 
Zhang Y, Wu Q, Zhang L, et al. Caffeic acid reduces A53T α-synuclein by activating JNK/Bcl-2-mediated autophagy in vitro and improves behaviour and protects dopaminergic neurons in a mouse model of Parkinson’s disease. Pharmacol Res  2019; 150: 104538.
[http://dx.doi.org/10.1016/j.phrs.2019.104538] [PMID: 31707034] 
[123] 
Zhou ZD, Selvaratnam T, Lee JCT, Chao YX, Tan EK. Molecular targets for modulating the protein translation vital to proteostasis and neuron degeneration in Parkinson’s disease. Transl Neurodegener  2019; 8: 6.
[http://dx.doi.org/10.1186/s40035-019-0145-0] [PMID: 30740222] 
[124] 
Hsieh CF, Liu CK, Lee CT, Yu LE, Wang JY. Acute glucose fluctuation impacts microglial activity, leading to inflammatory activation or self-degradation. Sci Rep  2019; 9(1): 840.
[http://dx.doi.org/10.1038/s41598-018-37215-0] [PMID: 30696869] 
[125] 
Zhou T, Zhuang J, Wang Z, et al. Glaucocalyxin A as a natural product increases amyloid β clearance and decreases tau phosphorylation involving the mammalian target of rapamycin signaling pathway. Neuroreport  2019; 30(4): 310-6.
[http://dx.doi.org/10.1097/WNR.0000000000001202] [PMID: 30688759] 
[126] 
François A, Terro F, Quellard N, et al. Impairment of autophagy in the central nervous system during lipopolysaccharide-induced inflammatory stress in mice. Mol Brain  2014; 7(1): 56.
[http://dx.doi.org/10.1186/s13041-014-0056-z] [PMID: 25169902] 
[127] 
Maiese K, Fox O. FoxO proteins in the nervous system. Anal Cell Pathol (Amst)  2015; 2015: 569392.
[http://dx.doi.org/10.1155/2015/569392] [PMID: 26171319] 
[128] 
Sullivan PM, Zhou X, Robins AM, et al. The ALS/FTLD associated protein C9orf72 associates with SMCR8 and WDR41 to regulate the autophagy-lysosome pathway. Acta Neuropathol Commun  2016; 4(1): 51.
[http://dx.doi.org/10.1186/s40478-016-0324-5] [PMID: 27193190] 
[129] 
Lee JH, Tecedor L, Chen YH, et al. Reinstating aberrant mTORC1 activity in Huntington’s disease mice improves disease phenotypes. Neuron  2015; 85(2): 303-15.
[http://dx.doi.org/10.1016/j.neuron.2014.12.019] [PMID: 25556834] 
[130] 
Ye Y, Zhang P, Qian Y, Yin B, Yan M. The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury. Stem Cells Int  2017; 2017: 4782820.
[http://dx.doi.org/10.1155/2017/4782820] [PMID: 28883836] 
[131] 
Zhang P, Ye Y, Qian Y, et al. The effect of pyrroloquinoline quinone on apoptosis and autophagy in traumatic brain injury. CNS Neurol Disord Drug Targets  2017; 16(6): 724-36.
[http://dx.doi.org/10.2174/1871527316666170124164306] [PMID: 28124619] 
[132] 
Maiese K. Healing the heart with sirtuins and mammalian forkhead transcription factors. Curr Neurovasc Res  2020; 17(1): 1-2.
[http://dx.doi.org/10.2174/1567202616999191209142915] [PMID: 31814554] 
[133] 
Pan YR, Song JY, Fan B, et al. mTOR may interact with PARP-1 to regulate visible light-induced parthanatos in photoreceptors. Cell Commun Signal  2020; 18(1): 27.
[http://dx.doi.org/10.1186/s12964-019-0498-0] [PMID: 32066462] 
[134] 
Potthast AB, Nebl J, Wasserfurth P, et al. Impact of nutrition on short-term exercise-induced sirtuin regulation: Vegans differ from omnivores and lacto-ovo vegetarians. Nutrients  2020; 12(4): E1004.
[http://dx.doi.org/10.3390/nu12041004] [PMID: 32260570] 
[135] 
Tang YL, Zhang CG, Liu H, et al. Ginsenoside Rg1 inhibits cell proliferation and induces markers of cell senescence in CD34+CD38- leukemia stem cells derived from KG1α acute myeloid leukemia cells by activating the Sirtuin 1 (SIRT1)/Tuberous Sclerosis Complex 2 (TSC2) signaling pathway. Med Sci Monit  2020; 26: e918207.
[http://dx.doi.org/10.12659/MSM.918207] [PMID: 32037392] 
[136] 
Zhang GZ, Deng YJ, Xie QQ, et al. Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function. Clin Chim Acta  2020; 508: 33-42.
[http://dx.doi.org/10.1016/j.cca.2020.04.016] [PMID: 32348785] 
[137] 
Maiese K, Chong ZZ, Shang YC, Wang S. Translating cell survival and cell longevity into treatment strategies with SIRT1. Rom J Morphol Embryol  2011; 52(4): 1173-85.
[PMID: 22203920] 
[138] 
Maiese K. SIRT1 and stem cells: In the forefront with cardiovascular disease, neurodegeneration and cancer. World J Stem Cells  2015; 7(2): 235-42.
[http://dx.doi.org/10.4252/wjsc.v7.i2.235] [PMID: 25815111] 
[139] 
Charles S, Raj V, Arokiaraj J, Mala K. Caveolin1/protein arginine methyltransferase1/sirtuin1 axis as a potential target against endothelial dysfunction. Pharmacol Res  2017; 119: 1-11.
[http://dx.doi.org/10.1016/j.phrs.2017.01.022] [PMID: 28126510] 
[140] 
Chong ZZ, Shang YC, Wang S, Maiese K. SIRT1: New avenues of discovery for disorders of oxidative stress. Expert Opin Ther Targets  2012; 16(2): 167-78.
[http://dx.doi.org/10.1517/14728222.2012.648926] [PMID: 22233091] 
[141] 
Cui L, Guo J, Zhang Q, et al. Erythropoietin activates SIRT1 to protect human cardiomyocytes against doxorubicin-induced mitochondrial dysfunction and toxicity. Toxicol Lett  2017; 275: 28-38.
[http://dx.doi.org/10.1016/j.toxlet.2017.04.018] [PMID: 28456571] 
[142] 
Geng C, Xu H, Zhang Y, et al. Retinoic acid ameliorates high-fat diet-induced liver steatosis through sirt1. Sci China Life Sci  2017; 60(11): 1234-41.
[http://dx.doi.org/10.1007/s11427-016-9027-6] [PMID: 28667519] 
[143] 
Maiese K. Forkhead transcription factors: New considerations for alzheimer’s disease and dementia. J Transl Sci  2016; 2(4): 241-7.
[http://dx.doi.org/10.15761/JTS.1000146] [PMID: 27390624] 
[144] 
Maiese K. Moving to the rhythm with clock (circadian) genes, autophagy, mTOR, and SIRT1 in degenerative disease and cancer. Curr Neurovasc Res  2017; 14(3): 299-304.
[http://dx.doi.org/10.2174/1567202614666170718092010] [PMID: 28721811] 
[145] 
Maiese K. Harnessing the power of SIRT1 and non-coding RNAs in vascular disease. Curr Neurovasc Res  2017; 14(1): 82-8.
[http://dx.doi.org/10.2174/1567202613666161129112822] [PMID: 27897112] 
[146] 
Maiese K. Novel treatment strategies for the nervous system: Circadian clock genes, non-coding RNAs, and Forkhead Transcription Factors. Curr Neurovasc Res  2018; 15(1): 81-91.
[http://dx.doi.org/10.2174/1567202615666180319151244] [PMID: 29557749] 
[147] 
Maiese K. Sirtuins: Developing innovative treatments for aged-related memory loss and alzheimer’s disease. Curr Neurovasc Res  2018; 15(4): 367-71.
[http://dx.doi.org/10.2174/1567202616666181128120003] [PMID: 30484407] 
[148] 
Joe Y, Chen Y, Park J, et al. Cross-talk between CD38 and TTP is essential for resolution of inflammation during microbial sepsis. Cell Rep  2020; 30(4): 1063-1076.e5.
[http://dx.doi.org/10.1016/j.celrep.2019.12.090] [PMID: 31995750] 
[149] 
Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J Biol Chem  2002; 277(47): 45099-107.
[http://dx.doi.org/10.1074/jbc.M205670200] [PMID: 12297502] 
[150] 
Cai AL, Zipfel GJ, Sheline CT. Zinc neurotoxicity is dependent on intracellular NAD levels and the sirtuin pathway. Eur J Neurosci  2006; 24(8): 2169-76.
[http://dx.doi.org/10.1111/j.1460-9568.2006.05110.x] [PMID: 17042794] 
[151] 
Porcu M, Chiarugi A. The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. Trends Pharmacol Sci  2005; 26(2): 94-103.
[http://dx.doi.org/10.1016/j.tips.2004.12.009] [PMID: 15681027] 
[152] 
Saunders LR, Verdin E. Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene  2007; 26(37): 5489-504.
[http://dx.doi.org/10.1038/sj.onc.1210616] [PMID: 17694089] 
[153] 
Maiese K. Sirtuin Biology in Medicine: Targeting New Avenues of Care in Development, Aging, and Disease. 2021. [Epub ahead of print].
[154] 
Han J, Shi S, Min L, Wu T, Xia W, Ying W. NAD+ treatment induces delayed autophagy in Neuro2a cells partially by increasing oxidative stress. Neurochem Res  2011; 36(12): 2270-7.
[http://dx.doi.org/10.1007/s11064-011-0551-x] [PMID: 21833846] 
[155] 
Kim SW, Lee JH, Moon JH, et al. Niacin alleviates TRAIL-mediated colon cancer cell death via autophagy flux activation. Oncotarget  2016; 7(4): 4356-68.
[http://dx.doi.org/10.18632/oncotarget.5374] [PMID: 26517672] 
[156] 
Qi Z, Xia J, Xue X, He Q, Ji L, Ding S. Long-term treatment with nicotinamide induces glucose intolerance and skeletal muscle lipotoxicity in normal chow-fed mice: Compared to diet-induced obesity. J Nutr Biochem  2016; 36: 31-41.
[http://dx.doi.org/10.1016/j.jnutbio.2016.07.005] [PMID: 27567590] 
[157] 
Audrito V, Vaisitti T, Rossi D, et al. Nicotinamide blocks proliferation and induces apoptosis of chronic lymphocytic leukemia cells through activation of the p53/miR-34a/SIRT1 tumor suppressor network. Cancer Res  2011; 71(13): 4473-83.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-4452] [PMID: 21565980] 
[158] 
Wang T, Cui H, Ma N, Jiang Y. Nicotinamide-mediated inhibition of SIRT1 deacetylase is associated with the viability of cancer cells exposed to antitumor agents and apoptosis. Oncol Lett  2013; 6(2): 600-4.
[http://dx.doi.org/10.3892/ol.2013.1400] [PMID: 24137378] 
[159] 
Zhang JG, Zhao G, Qin Q, Wang B, Liu L, Liu Y, et al. Nicotinamide prohibits proliferation and enhances chemosensitivity of pancreatic cancer cells through deregulating SIRT1 and Ras/Akt pathways. Pancreatology  2013; 13(2): 140-6.
[160] 
Maiese K. Sirtuin biology in cancer and metabolic disease: Cellular pathways for clinical discovery. USA: Academic Press 2021.
[161] 
Zhang XM, Jing YP, Jia MY, Zhang L. Negative transcriptional regulation of inflammatory genes by group B3 vitamin nicotinamide. Mol Biol Rep  2012; 39(12): 10367-71.
[http://dx.doi.org/10.1007/s11033-012-1915-2] [PMID: 23053940] 
[162] 
Shen C, Dou X, Ma Y, Ma W, Li S, Song Z. Nicotinamide protects hepatocytes against palmitate-induced lipotoxicity via SIRT1-dependent autophagy induction. Nutr Res  2017; 40: 40-7.
[http://dx.doi.org/10.1016/j.nutres.2017.03.005] [PMID: 28473059] 
[163] 
Johri MK, Lashkari HV, Gupta D, Vedagiri D, Harshan KH. mTORC1 restricts hepatitis C virus RNA replication through ULK1-mediated suppression of miR-122 and facilitates post-replication events. J Gen Virol  2020; 101(1): 86-95.
[http://dx.doi.org/10.1099/jgv.0.001356] [PMID: 31821132] 
[164] 
Maiese K. New challenges and strategies for cardiac disease: Autophagy, mTOR, and AMP-activated protein kinase. Curr Neurovasc Res  2020; 17(2): 111-2.
[http://dx.doi.org/10.2174/1567202617999200207153935] [PMID: 32036783] 
[165] 
Tian Y, Xiao YH, Geng T, et al. Clusterin suppresses spermatogenic cell apoptosis to alleviate diabetes-induced testicular damage by inhibiting autophagy via the PI3K/AKT/mTOR axis. Biol Cell  2020; 113(1): 14-27.
[http://dx.doi.org/10.1111/boc.202000030] [PMID: 32942336] 
[166] 
Tabibzadeh S. Signaling pathways and effectors of aging. Front Biosci  2021; 26: 50-96.
[http://dx.doi.org/10.2741/4889] [PMID: 33049665] 
[167] 
Blagosklonny MV. From causes of aging to death from COVID-19. Aging (Albany NY)  2020; 12(11): 10004-21.
[http://dx.doi.org/10.18632/aging.103493] [PMID: 32534452] 
[168] 
Maiese K. Dysregulation of metabolic flexibility: The impact of mTOR on autophagy in neurodegenerative disease. Int Rev Neurobiol  2020; 155: 1-35.
[http://dx.doi.org/10.1016/bs.irn.2020.01.009] [PMID: 32854851] 
[169] 
Saenwongsa W, Nithichanon A, Chittaganpitch M, et al. Metformin-induced suppression of IFN-α via mTORC1 signalling following seasonal vaccination is associated with impaired antibody responses in type 2 diabetes. Sci Rep  2020; 10(1): 3229.
[http://dx.doi.org/10.1038/s41598-020-60213-0] [PMID: 32094377] 
[170] 
Hwang SK, Kim HH. The functions of mTOR in ischemic diseases. BMB Rep  2011; 44(8): 506-11.
[http://dx.doi.org/10.5483/BMBRep.2011.44.8.506] [PMID: 21871173] 
[171] 
Maiese K. Erythropoietin and mTOR: A “One-Two Punch” for aging-related disorders accompanied by enhanced life expectancy. Curr Neurovasc Res  2016; 13(4): 329-40.
[http://dx.doi.org/10.2174/1567202613666160729164900] [PMID: 27488211] 
[172] 
Martínez de Morentin PB, Martinez-Sanchez N, Roa J, et al. Hypothalamic mTOR: the rookie energy sensor. Curr Mol Med  2014; 14(1): 3-21.
[http://dx.doi.org/10.2174/1566524013666131118103706] [PMID: 24236459] 
[173] 
Maiese K, Chong ZZ, Shang YC, Wang S. mTOR: On target for novel therapeutic strategies in the nervous system. Trends Mol Med  2013; 19(1): 51-60.
[http://dx.doi.org/10.1016/j.molmed.2012.11.001] [PMID: 23265840] 
[174] 
Maiese K. Driving neural regeneration through the mammalian target of rapamycin. Neural Regen Res  2014; 9(15): 1413-7.
[http://dx.doi.org/10.4103/1673-5374.139453] [PMID: 25317149] 
[175] 
Malla R, Ashby CR Jr, Narayanan NK, Narayanan B, Faridi JS, Tiwari AK. Proline-rich AKT substrate of 40-kDa (PRAS40) in the pathophysiology of cancer. Biochem Biophys Res Commun  2015; 463(3): 161-6.
[http://dx.doi.org/10.1016/j.bbrc.2015.05.041] [PMID: 26003731] 
[176] 
Chong ZZ, Shang YC, Wang S, Maiese K. Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin. Prog Neurobiol  2012; 99(2): 128-48.
[http://dx.doi.org/10.1016/j.pneurobio.2012.08.001] [PMID: 22980037] 
[177] 
Jacinto E, Loewith R, Schmidt A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol  2004; 6(11): 1122-8.
[http://dx.doi.org/10.1038/ncb1183] [PMID: 15467718] 
[178] 
Fu L, Liu C, Chen L, et al. Protective effects of 1-Methylnicotinamide on Abeta1-42-induced cognitive deficits, neuroinflammation and apoptosis in mice. J Neuroimmune Pharmacol  2019; 14(3): 401-12.
[179] 
Klimova N, Kristian T. Multi-targeted Effect of Nicotinamide Mononucleotide on Brain Bioenergetic Metabolism. Neurochem Res  2019; 44(10): 2280-7.
[http://dx.doi.org/10.1007/s11064-019-02729-0] [PMID: 30661231] 
[180] 
Li J, Lu Y, Li N, et al. Muscle metabolomics analysis reveals potential biomarkers of exercise-dependent improvement of the diaphragm function in chronic obstructive pulmonary disease. Int J Mol Med  2020; 45(6): 1644-60.
[http://dx.doi.org/10.3892/ijmm.2020.4537] [PMID: 32186768] 
[181] 
Alves OJ, Pereira ML, do Rego Monteiro ICC, et al. Strenuous acute exercise induces slow and fast twitch-dependent NADPH Oxidase expression in rat skeletal muscle. Antioxidants (Basel, Switzerland)  2020; 9
                    (1): 57.
[http://dx.doi.org/10.3390/antiox9010057] 
[182] 
Tong Y, Elkin KB, Peng C, et al. Reduced Apoptotic Injury by Phenothiazine in Ischemic Stroke through the NOX-Akt/PKC Pathway. Brain Sci  2019; 9(12): E378.
[http://dx.doi.org/10.3390/brainsci9120378] [PMID: 31847503] 
[183] 
Li W, Zhu L, Ruan ZB, Wang MX, Ren Y, Lu W. Nicotinamide protects chronic hypoxic myocardial cells through regulating mTOR pathway and inducing autophagy. Eur Rev Med Pharmacol Sci  2019; 23(12): 5503-11.
[PMID: 31298404] 
[184] 
Ka M, Smith AL, Kim WY. MTOR controls genesis and autophagy of GABAergic interneurons during brain development. Autophagy  2017; 13(8): 1348-63.
[http://dx.doi.org/10.1080/15548627.2017.1327927] 
[185] 
Kim KA, Shin YJ, Akram M, et al. High glucose condition induces autophagy in endothelial progenitor cells contributing to angiogenic impairment. Biol Pharm Bull  2014; 37(7): 1248-52.
[http://dx.doi.org/10.1248/bpb.b14-00172] [PMID: 24989016] 
[186] 
Yamada D, Kawabe K, Tosa I, et al. Inhibition of the glutamine transporter SNAT1 confers neuroprotection in mice by modulating the mTOR-autophagy system. Commun Biol  2019; 2: 346.
[http://dx.doi.org/10.1038/s42003-019-0582-4] [PMID: 31552299] 
[187] 
Borowicz-Reutt KK, Czuczwar SJ. Role of oxidative stress in epileptogenesis and potential implications for therapy. Pharmacol Rep  2020; 72(5): 1218-26.
[http://dx.doi.org/10.1007/s43440-020-00143-w] [PMID: 32865811] 
[188] 
Rey F, Balsari A, Giallongo T, et al. Erythropoietin as a neuroprotective molecule: An overview of its therapeutic potential in neurodegenerative diseases. ASN Neuro  2019; 2019: 11.
[http://dx.doi.org/10.1177/1759091419871420] [PMID: 31450955] 
[189] 
Maiese K. MicroRNAs for the treatment of dementia and alzheimer’s disease. Curr Neurovasc Res  2019; 16(1): 1-2.
[http://dx.doi.org/10.2174/1567202616666190208094159] [PMID: 30732557] 
[190] 
Maiese K. Impacting dementia and cognitive loss with innovative strategies: mechanistic target of rapamycin, clock genes, circular non-coding ribonucleic acids, and Rho/Rock. Neural Regen Res  2019; 14(5): 773-4.
[http://dx.doi.org/10.4103/1673-5374.249224] [PMID: 30688262] 
[191] 
Xu F, Na L, Li Y, Chen L. Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours. Cell Biosci  2020; 10: 54.
[http://dx.doi.org/10.1186/s13578-020-00416-0] [PMID: 32266056] 
[192] 
World Health Organization. Global action plan on the public health response to dementia 2017-2025. 2017; 1-44.
[193] 
Albiero M, Poncina N, Tjwa M, et al. Diabetes causes bone marrow autonomic neuropathy and impairs stem cell mobilization via dysregulated p66Shc and Sirt1. Diabetes  2014; 63(4): 1353-65.
[http://dx.doi.org/10.2337/db13-0894] [PMID: 24270983] 
[194] 
Gomes MB, Negrato CA. Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases. Diabetol Metab Syndr  2014; 6(1): 80.
[http://dx.doi.org/10.1186/1758-5996-6-80] [PMID: 25104975] 
[195] 
Gomez-Brouchet A, Blaes N, Mouledous L, et al. Beneficial effects of levobupivacaine regional anaesthesia on postoperative opioid induced hyperalgesia in diabetic mice. J Transl Med  2015; 13(1): 208.
[http://dx.doi.org/10.1186/s12967-015-0575-0] [PMID: 26136113] 
[196] 
Atef MM, El-Sayed NM, Ahmed AAM, Mostafa YM. Donepezil improves neuropathy through activation of AMPK signalling pathway in streptozotocin-induced diabetic mice. Biochem Pharmacol  2019; 159: 1-10.
[http://dx.doi.org/10.1016/j.bcp.2018.11.006] [PMID: 30414938] 
[197] 
Dong J, Li H, Bai Y, Wu C. Muscone ameliorates diabetic peripheral neuropathy through activating AKT/mTOR signalling pathway. J Pharm Pharmacol  2019; 71(11): 1706-13.
[http://dx.doi.org/10.1111/jphp.13157] [PMID: 31468549] 
[198] 
Caberlotto L, Nguyen TP, Lauria M, et al. Cross-disease analysis of Alzheimer’s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases. Sci Rep  2019; 9(1): 3965.
[http://dx.doi.org/10.1038/s41598-019-39828-5] [PMID: 30850634] 
[199] 
Su M, Naderi K, Samson N, et al. Mechanisms associated with Type 2 diabetes as a risk factor for alzheimer-related pathology. Mol Neurobiol  2019; 56(8): 5815-34.
[http://dx.doi.org/10.1007/s12035-019-1475-8] [PMID: 30684218] 
[200] 
Hu Z, Jiao R, Wang P, et al. Shared causal paths underlying Alzheimer’s dementia and Type 2 Diabetes. Sci Rep  2020; 10(1): 4107.
[http://dx.doi.org/10.1038/s41598-020-60682-3] [PMID: 32139775] 
[201] 
Maiese K, Chong ZZ, Shang YC, Hou J. FoxO proteins: Cunning concepts and considerations for the cardiovascular system. Clin Sci (Lond)  2009; 116(3): 191-203.
[http://dx.doi.org/10.1042/CS20080113] [PMID: 19118491] 
[202] 
Tang PC, Ng YF, Ho S, Gyda M, Chan SW. Resveratrol and cardiovascular health--promising therapeutic or hopeless illusion? Pharmacol Res  2014; 90: 88-115.
[http://dx.doi.org/10.1016/j.phrs.2014.08.001] [PMID: 25151891] 
[203] 
Xiang L, Mittwede PN, Clemmer JS. Glucose homeostasis and cardiovascular alterations in diabetes. Compr Physiol  2015; 5(4): 1815-39.
[http://dx.doi.org/10.1002/cphy.c150001] [PMID: 26426468] 
[204] 
Xu YJ, Tappia PS, Neki NS, Dhalla NS. Prevention of diabetes-induced cardiovascular complications upon treatment with antioxidants. Heart Fail Rev  2014; 19(1): 113-21.
[http://dx.doi.org/10.1007/s10741-013-9379-6] [PMID: 23436032] 
[205] 
Yao T, Fujimura T, Murayama K, Okumura K, Seko Y. Oxidative Stress-Responsive Apoptosis Inducing Protein (ORAIP) plays a critical role in high glucose-induced apoptosis in rat cardiac myocytes and murine pancreatic β-cells. Cells  2017; 6(4): 35.
[http://dx.doi.org/10.3390/cells6040035] [PMID: 29057797] 
[206] 
Fan X, Zhao Z, Wang D, Xiao J. Glycogen synthase kinase-3 as a key regulator of cognitive function. Acta Biochim Biophys Sin (Shanghai)  2020; 52(3): 219-30.
[http://dx.doi.org/10.1093/abbs/gmz156] [PMID: 32147679] 
[207] 
Hadamitzky M, Herring A, Kirchhof J, et al. Repeated systemic treatment with rapamycin affects behavior and amygdala protein expression in rats. Int J Neuropsychopharmacol  2018; 21(6): 592-602.
[http://dx.doi.org/10.1093/ijnp/pyy017] [PMID: 29462337] 
[208] 
Ignácio ZM, Réus GZ, Arent CO, Abelaira HM, Pitcher MR, Quevedo J. New perspectives on the involvement of mTOR in depression as well as in the action of antidepressant drugs. Br J Clin Pharmacol  2016; 82(5): 1280-90.
[http://dx.doi.org/10.1111/bcp.12845] [PMID: 26613210] 
[209] 
Di Rosa M, Malaguarnera L. Chitotriosidase: A new inflammatory marker in diabetic complications. Pathobiology  2016; 83(4): 211-9.
[http://dx.doi.org/10.1159/000443932] [PMID: 27116685] 
[210] 
Maiese K, Chong ZZ, Hou J, Shang YC. Erythropoietin and oxidative stress. Curr Neurovasc Res  2008; 5(2): 125-42.
[http://dx.doi.org/10.2174/156720208784310231] [PMID: 18473829] 
[211] 
Tulsulkar J, Nada SE, Slotterbeck BD, McInerney MF, Shah ZA. Obesity and hyperglycemia lead to impaired post-ischemic recovery after permanent ischemia in mice. Obesity (Silver Spring, Md)  2015; 24(2): 417-23.
[212] 
Xiao FH, He YH, Li QG, Wu H, Luo LH, Kong QP. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes. PLoS One  2015; 10(3): e0120388.
[http://dx.doi.org/10.1371/journal.pone.0120388] [PMID: 25793257] 
[213] 
Yuan X, Liu Y, Bijonowski BM, et al. NAD+/NADH redox alterations reconfigure metabolism and rejuvenate senescent human mesenchymal stem cells in vitro. Commun Biol  2020; 3(1): 774.
[http://dx.doi.org/10.1038/s42003-020-01514-y] [PMID: 33319867] 
[214] 
Arildsen L, Andersen JV, Waagepetersen HS, Nissen JBD, Sheykhzade M. Hypermetabolism and impaired endothelium-dependent vasodilation in mesenteric arteries of type 2 diabetes mellitus db/db mice. Diab Vasc Dis Res  2019; 16(6): 539-48.
[http://dx.doi.org/10.1177/1479164119865885] [PMID: 31364402] 
[215] 
Ding S, Zhu Y, Liang Y, Huang H, Xu Y, Zhong C. Circular RNAs in Vascular Functions and Diseases. Adv Exp Med Biol  2018; 1087: 287-97.
[http://dx.doi.org/10.1007/978-981-13-1426-1_23] [PMID: 30259375] 
[216] 
Pal PB, Sonowal H, Shukla K, Srivastava SK, Ramana KV. Aldose reductase regulates hyperglycemia-induced HUVEC death via SIRT1/AMPK-α1/mTOR pathway. J Mol Endocrinol  2019; 63(1): 11-25.
[http://dx.doi.org/10.1530/JME-19-0080] [PMID: 30986766] 
[217] 
Alexandru N, Popov D, Georgescu A. Platelet dysfunction in vascular pathologies and how can it be treated. Thromb Res  2012; 129(2): 116-26.
[http://dx.doi.org/10.1016/j.thromres.2011.09.026] [PMID: 22035630] 
[218] 
Barchetta I, Cimini FA, Ciccarelli G, Baroni MG, Cavallo MG. Sick fat: The good and the bad of old and new circulating markers of adipose tissue inflammation. J Endocrinol Invest  2019; 42(11): 1257-72.
[http://dx.doi.org/10.1007/s40618-019-01052-3] [PMID: 31073969] 
[219] 
Chiu SC, Chao CY, Chiang EI, Syu JN, Rodriguez RL, Tang FY. N-3 polyunsaturated fatty acids alleviate high glucose-mediated dysfunction of endothelial progenitor cells and prevent ischemic injuries both in vitro and in vivo. J Nutr Biochem  2017; 42: 172-81.
[http://dx.doi.org/10.1016/j.jnutbio.2017.01.009] [PMID: 28189115] 
[220] 
Maiese K. Disease onset and aging in the world of circular RNAs. J Transl Sci  2016; 2(6): 327-9.
[http://dx.doi.org/10.15761/JTS.1000158] [PMID: 27642518] 
[221] 
Maiese K, Chong ZZ, Shang YC. Mechanistic insights into diabetes mellitus and oxidative stress. Curr Med Chem  2007; 14(16): 1729-38.
[http://dx.doi.org/10.2174/092986707781058968] [PMID: 17627510] 
[222] 
Maiese K, Chong ZZ, Shang YC, Hou J. Rogue proliferation versus restorative protection: where do we draw the line for Wnt and forkhead signaling? Expert Opin Ther Targets  2008; 12(7): 905-16.
[http://dx.doi.org/10.1517/14728222.12.7.905] [PMID: 18554157] 
[223] 
Pérez-Hernández N, Vargas-Alarcón G, Posadas-Sánchez R, et al. PHACTR1 gene polymorphism is associated with increased risk of developing premature coronary artery disease in Mexican population. Int J Environ Res Public Health  2016; 13(8): 803.
[http://dx.doi.org/10.3390/ijerph13080803] [PMID: 27517945] 
[224] 
Thackeray JT, Radziuk J, Harper ME, et al. Sympathetic nervous dysregulation in the absence of systolic left ventricular dysfunction in a rat model of insulin resistance with hyperglycemia. Cardiovasc Diabetol  2011; 10: 75.
[http://dx.doi.org/10.1186/1475-2840-10-75] [PMID: 21831292] 
[225] 
Mishra M, Duraisamy AJ, Kowluru RA. Sirt1: A guardian of the development of diabetic retinopathy. Diabetes  2018; 67(4): 745-54.
[http://dx.doi.org/10.2337/db17-0996] [PMID: 29311218] 
[226] 
Ponnalagu M, Subramani M, Jayadev C, Shetty R, Das D. Retinal pigment epithelium-secretome: A diabetic retinopathy perspective. Cytokine  2017; 95: 126-35.
[http://dx.doi.org/10.1016/j.cyto.2017.02.013] [PMID: 28282610] 
[227] 
Kell DB, Pretorius E. No effects without causes: The Iron dysregulation and dormant microbes hypothesis for chronic, inflammatory diseases. Biol Rev Camb Philos Soc  2018; 93(3): 1518-57.
[http://dx.doi.org/10.1111/brv.12407] [PMID: 29575574] 
[228] 
Lin X, Zhang N. Berberine: Pathways to protect neurons. Phytotherapy research : PTR  2018; 32(10): 1501-10.
[229] 
Maiese K, Fox O. FoxO Transcription factors and regenerative pathways in diabetes mellitus. Curr Neurovasc Res  2015; 12(4): 404-13.
[http://dx.doi.org/10.2174/1567202612666150807112524] [PMID: 26256004] 
[230] 
Woodhams L, Al-Salami H. The roles of bile acids and applications of microencapsulation technology in treating Type 1 diabetes mellitus. Ther Deliv  2017; 8(6): 401-9.
[http://dx.doi.org/10.4155/tde-2017-0010] [PMID: 28530150] 
[231] 
Zhao Y, Scott NA, Fynch S, et al. Autoreactive T cells induce necrosis and not BCL-2-regulated or death receptor-mediated apoptosis or RIPK3-dependent necroptosis of transplanted islets in a mouse model of type 1 diabetes. Diabetologia  2015; 58(1): 140-8.
[http://dx.doi.org/10.1007/s00125-014-3407-5] [PMID: 25301392] 
[232] 
Anderson DW, Bradbury KA, Schneider JS. Neuroprotection in Parkinson models varies with toxin administration protocol. Eur J Neurosci  2006; 24(11): 3174-82.
[http://dx.doi.org/10.1111/j.1460-9568.2006.05192.x] [PMID: 17156378] 
[233] 
Feng Y, Paul IA, LeBlanc MH. Nicotinamide reduces hypoxic ischemic brain injury in the newborn rat. Brain Res Bull  2006; 69(2): 117-22.
[http://dx.doi.org/10.1016/j.brainresbull.2005.11.011] [PMID: 16533659] 
[234] 
Slomka M, Zieminska E, Salinska E, Lazarewicz JW. Neuroprotective effects of nicotinamide and 1-methylnicotinamide in acute excitotoxicity in vitro. Folia Neuropathol  2008; 46(1): 69-80.
[PMID: 18368629] 
[235] 
Slomka M, Zieminska E, Lazarewicz J. Nicotinamide and 1-methylnicotinamide reduce homocysteine neurotoxicity in primary cultures of rat cerebellar granule cells. Acta Neurobiol Exp (Warsz)  2008; 68(1): 1-9.
[PMID: 18389009] 
[236] 
Shen CC, Huang HM, Ou HC, Chen HL, Chen WC, Jeng KC. Protective effect of nicotinamide on neuronal cells under oxygen and glucose deprivation and hypoxia/reoxygenation. J Biomed Sci  2004; 11(4): 472-81.
[http://dx.doi.org/10.1007/BF02256096] [PMID: 15153782] 
[237] 
Turunc Bayrakdar E, Uyanikgil Y, Kanit L, Koylu E, Yalcin A. Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ(1-42)-induced rat model of Alzheimer’s disease. Free Radic Res  2014; 48(2): 146-58.
[http://dx.doi.org/10.3109/10715762.2013.857018] [PMID: 24151909] 
[238] 
Itzhaki O, Greenberg E, Shalmon B, et al. Nicotinamide inhibits vasculogenic mimicry, an alternative vascularization pathway observed in highly aggressive melanoma. PLoS One  2013; 8(2): e57160.
[http://dx.doi.org/10.1371/journal.pone.0057160] [PMID: 23451174] 
[239] 
Shear DA, Dixon CE, Bramlett HM, et al. Nicotinamide treatment in traumatic brain injury: Operation brain trauma therapy. J Neurotrauma  2016; 33(6): 523-37.
[http://dx.doi.org/10.1089/neu.2015.4115] [PMID: 26670792] 
[240] 
Kiuchi K, Yoshizawa K, Shikata N, Matsumura M, Tsubura A. Nicotinamide prevents N-methyl-N-nitrosourea-induced photoreceptor cell apoptosis in Sprague-Dawley rats and C57BL mice. Exp Eye Res  2002; 74(3): 383-92.
[http://dx.doi.org/10.1006/exer.2001.1127] [PMID: 12014919] 
[241] 
Peterson TC, Hoane MR, McConomy K, et al. A combination therapy of Nicotinamide and progesterone improves functional recovery following traumatic brain injury. J Neurotrauma  2015; 32(11): 765-9.
[PMID: 25313690] 
[242] 
Wang J, Zhai Q, Chen Y, et al. A local mechanism mediates NAD-dependent protection of axon degeneration. J Cell Biol  2005; 170(3): 349-55.
[http://dx.doi.org/10.1083/jcb.200504028] [PMID: 16043516] 
[243] 
Brewer KL, Hardin JS. Neuroprotective effects of nicotinamide after experimental spinal cord injury. Acad Emerg Med  2004; 11(2): 125-30.
[http://dx.doi.org/10.1197/j.aem.2003.09.010] [PMID: 14759952] 
[244] 
Isbir CS, Ak K, Kurtkaya O, et al. Ischemic preconditioning and nicotinamide in spinal cord protection in an experimental model of transient aortic occlusion. Eur J Cardiothorac Surg  2003; 23(6): 1028-33.
[http://dx.doi.org/10.1016/S1010-7940(03)00110-6] [PMID: 12829083] 
[245] 
Ullah N, Lee HY, Naseer MI, Ullah I, Suh JW, Kim MO. Nicotinamide inhibits alkylating agent-induced apoptotic neurodegeneration in the developing rat brain. PLoS One  2011; 6(12): e27093.
[http://dx.doi.org/10.1371/journal.pone.0027093] [PMID: 22164206] 
[246] 
Anderson DW, Bradbury KA, Schneider JS. Broad neuroprotective profile of nicotinamide in different mouse models of MPTP-induced parkinsonism. Eur J Neurosci  2008; 28(3): 610-7.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06356.x] [PMID: 18702732] 
[247] 
Williams A, Ramsden D. Nicotinamide: A double edged sword. Parkinsonism Relat Disord  2005; 11(7): 413-20.
[http://dx.doi.org/10.1016/j.parkreldis.2005.05.011] [PMID: 16183323] 
[248] 
Williams AC, Cartwright LS, Ramsden DB. Parkinson’s disease: The first common neurological disease due to auto-intoxication? QJM  2005; 98(3): 215-26.
[http://dx.doi.org/10.1093/qjmed/hci027] [PMID: 15728403] 
[249] 
Chong ZZ, Li F, Maiese K. Oxidative stress in the brain: novel cellular targets that govern survival during neurodegenerative disease. Prog Neurobiol  2005; 75(3): 207-46.
[http://dx.doi.org/10.1016/j.pneurobio.2005.02.004] [PMID: 15882775] 
[250] 
Zhang F, Hu Y, Xu X, et al. Icariin protects against intestinal ischemia-reperfusion injury. J Surg Res  2015; 194(1): 127-38.
[http://dx.doi.org/10.1016/j.jss.2014.10.004] [PMID: 25472572] 
[251] 
Czubowicz K, Jęśko H, Wencel P, Lukiw WJ, Strosznajder RP. The role of Ceramide and Sphingosine-1-Phosphate in Alzheimer’s disease and other neurodegenerative disorders. Mol Neurobiol  2019; 56(8): 5436-55.
[http://dx.doi.org/10.1007/s12035-018-1448-3] [PMID: 30612333] 
[252] 
Sanphui P, Das AK, Biswas SC. FoxO3a requires BAF57, a subunit of chromatin remodeler SWI/SNF complex for induction of PUMA in a model of Parkinson’s disease. J Neurochem  2020; 154(5): e14969.
[http://dx.doi.org/10.1111/jnc.14969] [PMID: 31971251] 
[253] 
Maiese K, Chong ZZ, Shang YC. OutFOXOing disease and disability: The therapeutic potential of targeting FoxO proteins. Trends Mol Med  2008; 14(5): 219-27.
[http://dx.doi.org/10.1016/j.molmed.2008.03.002] [PMID: 18403263] 
[254] 
Maiese K, Chong ZZ, Shang YC. “Sly as a FOXO”: New paths with Forkhead signaling in the brain. Curr Neurovasc Res  2007; 4(4): 295-302.
[http://dx.doi.org/10.2174/156720207782446306] [PMID: 18045156] 
[255] 
Sooknual P, Pingaew R, Phopin K, et al. Synthesis and neuroprotective effects of novel chalcone-triazole hybrids. Bioorg Chem  2020; 105: 104384.
[http://dx.doi.org/10.1016/j.bioorg.2020.104384] [PMID: 33130346] 
[256] 
Wang Y, Lin Y, Wang L, et al. TREM2 ameliorates neuroinflammatory response and cognitive impairment via PI3K/AKT/FoxO3a signaling pathway in Alzheimer’s disease mice. Aging (Albany NY)  2020; 12(20): 20862-79.
[http://dx.doi.org/10.18632/aging.104104] [PMID: 33065553] 
[257] 
Maiese K, Chong ZZ, Shang YC, Hou J. A “FOXO” in sight: Targeting Foxo proteins from conception to cancer. Med Res Rev  2009; 29(3): 395-418.
[http://dx.doi.org/10.1002/med.20139] [PMID: 18985696] 
[258] 
Liu W, Li Y, Luo B. Current perspective on the regulation of FOXO4 and its role in disease progression. Cell Mol Life Sci  2020; 77(4): 651-63.
[http://dx.doi.org/10.1007/s00018-019-03297-w] [PMID: 31529218] 
[259] 
Peng S, Li W, Hou N, Huang N. A review of FoxO1-regulated metabolic diseases and related drug discoveries. Cells  2020; 9(1): 184.
[http://dx.doi.org/10.3390/cells9010184] [PMID: 31936903] 
[260] 
Yaman D, Takmaz T, Yüksel N, Dinçer SA, Şahin Fİ. Evaluation of silent information regulator T (SIRT) 1 and Forkhead Box O (FOXO) transcription factor 1 and 3a genes in glaucoma. Mol Biol Rep  2020; 47(12): 9337-44.
[http://dx.doi.org/10.1007/s11033-020-05994-3] [PMID: 33200312] 
[261] 
Zhang W, Bai S, Yang J, et al. FoxO1 overexpression reduces Aβ production and tau phosphorylation in vitro. Neurosci Lett  2020; 738: 135322.
[http://dx.doi.org/10.1016/j.neulet.2020.135322] [PMID: 32860886] 
[262] 
Tsai KL, Sun YJ, Huang CY, Yang JY, Hung MC, Hsiao CD. Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification. Nucleic Acids Res  2007; 35(20): 6984-94.
[http://dx.doi.org/10.1093/nar/gkm703] [PMID: 17940099] 
[263] 
Scodelaro Bilbao P, Boland R. Extracellular ATP regulates FoxO family of transcription factors and cell cycle progression through PI3K/Akt in MCF-7 cells. Biochim Biophys Acta  2013; 1830(10): 4456-69.
[http://dx.doi.org/10.1016/j.bbagen.2013.05.034] [PMID: 23742826] 
[264] 
Maiese K, Li F, Chong ZZ. Erythropoietin in the brain: Can the promise to protect be fulfilled? Trends Pharmacol Sci  2004; 25(11): 577-83.
[http://dx.doi.org/10.1016/j.tips.2004.09.006] [PMID: 15491780] 
[265] 
Charvet C, Alberti I, Luciano F, et al. Proteolytic regulation of forkhead transcription factor FOXO3a by caspase-3-like proteases. Oncogene  2003; 22(29): 4557-68.
[http://dx.doi.org/10.1038/sj.onc.1206778] [PMID: 12881712] 
[266] 
Klimontov VV, Bulumbaeva DM, Fazullina ON, et al. Circulating Wnt1-inducible signaling pathway protein-1 (WISP-1/CCN4) is a novel biomarker of adiposity in subjects with type 2 diabetes. J Cell Commun Signal  2020; 14(1): 101-9.
[http://dx.doi.org/10.1007/s12079-019-00536-4] [PMID: 31782053] 
[267] 
Maiese K. Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR. Neural Regen Res  2016; 11(3): 372-85.
[http://dx.doi.org/10.4103/1673-5374.179032] [PMID: 27127460] 
[268] 
Centers for Disease Control and Prevention. National Diabetes Statistics Report 2020; 2020: 1-30.
[269] 
Liu L, Hu J, Yang L, et al. Association of WISP1/CCN4 with risk of overweight and gestational Diabetes Mellitus in Chinese pregnant women. Dis Markers  2020; 2020: 4934206.
[http://dx.doi.org/10.1155/2020/4934206] [PMID: 32377270] 
[270] 
Zaiou M. circRNAs signature as potential diagnostic and prognostic biomarker for Diabetes mellitus and related cardiovascular complications. Cells  2020; 9(3): E659.
[http://dx.doi.org/10.3390/cells9030659] [PMID: 32182790] 
[271] 
Haldar SR, Chakrabarty A, Chowdhury S, Haldar A, Sengupta S, Bhattacharyya M. Oxidative stress-related genes in type 2 diabetes: Association analysis and their clinical impact. Biochem Genet  2015; 53(4-6): 93-119.
[http://dx.doi.org/10.1007/s10528-015-9675-z] [PMID: 25991559] 
[272] 
Jia G, Aroor AR, Martinez-Lemus LA, Sowers JR. Overnutrition, mTOR signaling, and cardiovascular diseases. Am J Physiol Regul Integr Comp Physiol  2014; 307(10): R1198-206.
[http://dx.doi.org/10.1152/ajpregu.00262.2014] [PMID: 25253086] 
[273] 
Ye Q, Fu JF. Paediatric type 2 diabetes in China-Pandemic, progression, and potential solutions. Pediatr Diabetes  2018; 19(1): 27-35.
[http://dx.doi.org/10.1111/pedi.12517] [PMID: 28326652] 
[274] 
International Diabetes Federation. Diabetes 9th ed IDF Diabetes Atlas.  2019.
[275] 
Harris MI, Eastman RC. Early detection of undiagnosed diabetes mellitus: A US perspective. Diabetes Metab Res Rev  2000; 16(4): 230-6.
[http://dx.doi.org/10.1002/1520-7560(2000)9999:9999<::AID-DMRR122>3.0.CO;2-W] [PMID: 10934451] 
[276] 
Maiese K. Heightened attention for Wnt signaling in Diabetes mellitus. Curr Neurovasc Res  2020; 17(3): 215-7.
[http://dx.doi.org/10.2174/1567202617999200327134835] [PMID: 32216737] 
[277] 
Cernea M, Tang W, Guan H, Yang K. Wisp1 mediates Bmp3-stimulated mesenchymal stem cell proliferation. J Mol Endocrinol  2016; 56(1): 39-46.
[http://dx.doi.org/10.1530/JME-15-0217] [PMID: 26489765] 
[278] 
Curjuric I, Imboden M, Bridevaux PO, et al. Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline. Age (Dordr)  2016; 38(3): 52.
[http://dx.doi.org/10.1007/s11357-016-9917-y] [PMID: 27125385] 
[279] 
Hill JH, Solt C, Foster MT. Obesity associated disease risk: the role of inherent differences and location of adipose depots. Horm Mol Biol Clin Investig  2018; 33(2): 12.
[http://dx.doi.org/10.1515/hmbci-2018-0012] [PMID: 29547393] 
[280] 
Liu Z, Gan L, Zhang T, Ren Q, Sun C. Melatonin alleviates adipose inflammation through elevating α-ketoglutarate and diverting adipose-derived exosomes to macrophages in mice. J Pineal Res  2018; 64(1): 12455.
[http://dx.doi.org/10.1111/jpi.12455] [PMID: 29149454] 
[281] 
Maiese K. Picking a bone with WISP1 (CCN4): New strategies against degenerative joint disease. J Transl Sci  2016; 1(3): 83-5.
[http://dx.doi.org/10.15761/JTS.1000120] [PMID: 26893943] 
[282] 
Mehta J, Rayalam S, Wang X. Cytoprotective effects of natural compounds against oxidative stress. Antioxidants  2018; 7(10): 147.
[http://dx.doi.org/10.3390/antiox7100147] [PMID: 30347819] 
[283] 
Wang AR, Yan XQ, Zhang C, Du CQ, Long WJ, Zhan D, et al. Characterization of Wnt1-inducible signaling pathway protein-1 in obese children and adolescents. Curr Med Sci  2018; 38(5): 868-74.
[http://dx.doi.org/10.1007/s11596-018-1955-5] 
[284] 
Centers for Medicare and Medicaid Services. National Health Expenditure Projections 2018-2027. 2019.
[285] 
Maiese K, Chong ZZ, Shang YC, Wang S. Novel directions for diabetes mellitus drug discovery. Expert Opin Drug Discov  2013; 8(1): 35-48.
[http://dx.doi.org/10.1517/17460441.2013.736485] [PMID: 23092114] 
[286] 
Ahangarpour A, Ramezani Ali Akbari F, Fathi Moghadam H. Effect of C-peptide alone or in combination with Nicotinamide on glucose and insulin levels in Streptozotocin-Nicotinamide-induced Type 2 diabetic mice. Malays J Med Sci  2014; 21(4): 12-7.
[PMID: 25977616] 
[287] 
Folwarczna J, Janas A, Cegieła U, et al. Caffeine at a moderate dose did not affect the skeletal system of rats with Streptozotocin-induced diabetes. Nutrients  2017; 9(11): 1196.
[http://dx.doi.org/10.3390/nu9111196] [PMID: 29084147] 
[288] 
Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiol Hung  2014; 101(4): 408-20.
[http://dx.doi.org/10.1556/APhysiol.101.2014.4.2] [PMID: 25532953] 
[289] 
Guo S, Chen Q, Sun Y, Chen J. Nicotinamide protects against skeletal muscle atrophy in streptozotocin-induced diabetic mice. Arch Physiol Biochem  2019; 125(5): 470-7.
[http://dx.doi.org/10.1080/13813455.2019.1638414] [PMID: 31291133] 
[290] 
Lee HJ, Yang SJ. Supplementation with Nicotinamide Riboside reduces brain inflammation and improves cognitive function in diabetic mice. Int J Mol Sci  2019; 20(17): E4196.
[http://dx.doi.org/10.3390/ijms20174196] [PMID: 31461911] 
[291] 
Reddy S, Bibby NJ, Wu D, Swinney C, Barrow G, Elliott RB. A combined casein-free-nicotinamide diet prevents diabetes in the NOD mouse with minimum insulitis. Diabetes Res Clin Pract  1995; 29(2): 83-92.
[http://dx.doi.org/10.1016/0168-8227(95)01109-9] [PMID: 8591703] 
[292] 
Hu Y, Wang Y, Wang L, et al. Effects of nicotinamide on prevention and treatment of streptozotocin-induced diabetes mellitus in rats. Chin Med J (Engl)  1996; 109(11): 819-22.
[PMID: 9275363] 
[293] 
Chlopicki S, Swies J, Mogielnicki A, et al. 1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. Br J Pharmacol  2007; 152(2): 230-9.
[http://dx.doi.org/10.1038/sj.bjp.0707383] [PMID: 17641676] 
[294] 
Hara N, Yamada K, Shibata T, Osago H, Hashimoto T, Tsuchiya M. Elevation of cellular NAD levels by nicotinic acid and involvement of nicotinic acid phosphoribosyltransferase in human cells. J Biol Chem  2007; 282(34): 24574-82.
[http://dx.doi.org/10.1074/jbc.M610357200] [PMID: 17604275] 
[295] 
Tam D, Tam M, Maynard KI. Nicotinamide modulates energy utilization and improves functional recovery from ischemia in the in vitro rabbit retina. Ann N Y Acad Sci  2005; 1053: 258-68.
[http://dx.doi.org/10.1196/annals.1344.023] [PMID: 16179531] 
[296] 
Olmos PR, Hodgson MI, Maiz A, et al. Nicotinamide protected first-phase insulin response (FPIR) and prevented clinical disease in first-degree relatives of type-1 diabetics. Diabetes Res Clin Pract  2006; 71(3): 320-33.
[http://dx.doi.org/10.1016/j.diabres.2005.07.009] [PMID: 16233932] 
[297] 
Crinó A, Schiaffini R, Ciampalini P, et al. IMDIAB Group. A two year observational study of nicotinamide and intensive insulin therapy in patients with recent onset type 1 diabetes mellitus. J Pediatr Endocrinol Metab  2005; 18(8): 749-54.
[http://dx.doi.org/10.1515/JPEM.2005.18.8.749] [PMID: 16200840] 
[298] 
Liu HK, Green BD, Flatt PR, McClenaghan NH, McCluskey JT. Effects of long-term exposure to nicotinamide and sodium butyrate on growth, viability, and the function of clonal insulin secreting cells. Endocr Res  2004; 30(1): 61-8.
[http://dx.doi.org/10.1081/ERC-120028485] [PMID: 15098920] 
[299] 
Reddy S, Salari-Lak N, Sandler S. Long-term effects of nicotinamide-induced inhibition of poly(adenosine diphosphate-ribose) polymerase activity in rat pancreatic islets exposed to interleukin-1 beta. Endocrinology  1995; 136(5): 1907-12.
[http://dx.doi.org/10.1210/endo.136.5.7720637] [PMID: 7720637] 
[300] 
Gaudineau C, Auclair K. Inhibition of human P450 enzymes by nicotinic acid and nicotinamide. Biochem Biophys Res Commun  2004; 317(3): 950-6.
[http://dx.doi.org/10.1016/j.bbrc.2004.03.137] [PMID: 15081432] 
[301] 
Lin F, Xu W, Guan C, et al. Niacin protects against UVB radiation-induced apoptosis in cultured human skin keratinocytes. Int J Mol Med  2012; 29(4): 593-600.
[http://dx.doi.org/10.3892/ijmm.2012.886] [PMID: 22246168] 
[302] 
Hamada S, Hara K, Hamada T, et al. Upregulation of the mammalian target of rapamycin complex 1 pathway by Ras homolog enriched in brain in pancreatic beta-cells leads to increased beta-cell mass and prevention of hyperglycemia. Diabetes  2009; 58(6): 1321-32.
[http://dx.doi.org/10.2337/db08-0519] [PMID: 19258434] 
[303] 
Fraenkel M, Ketzinel-Gilad M, Ariav Y, et al. mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes  2008; 57(4): 945-57.
[http://dx.doi.org/10.2337/db07-0922] [PMID: 18174523] 
[304] 
Sataranatarajan K, Ikeno Y, Bokov A, et al. Rapamycin Increases Mortality in db/db Mice, a Mouse Model of Type 2 Diabetes. J Gerontol A Biol Sci Med Sci  2016; 71(7): 850-7.
[http://dx.doi.org/10.1093/gerona/glv170] [PMID: 26442901] 
[305] 
Deblon N, Bourgoin L, Veyrat-Durebex C, et al. Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol  2012; 165(7): 2325-40.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01716.x] [PMID: 22014210] 
[306] 
Kang S, Chemaly ER, Hajjar RJ, Lebeche D. Resistin promotes cardiac hypertrophy via the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) and c-Jun N-terminal kinase/insulin receptor substrate 1 (JNK/IRS1) pathways. J Biol Chem  2011; 286(21): 18465-73.
[http://dx.doi.org/10.1074/jbc.M110.200022] [PMID: 21478152] 
[307] 
Liu P, Yang X, Hei C, et al. Rapamycin reduced ischemic brain damage in diabetic animals is associated with suppressions of mTOR and ERK1/2 signaling. Int J Biol Sci  2016; 12(8): 1032-40.
[http://dx.doi.org/10.7150/ijbs.15624] [PMID: 27489506] 
[308] 
Zhao Z, Liu H, Guo D. Aliskiren attenuates cardiac dysfunction by modulation of the mTOR and apoptosis pathways. Braz J Med Biol Res  2020; 53(2): e8793.
[http://dx.doi.org/10.1590/1414-431x20198793] [PMID: 31994601] 
[309] 
Gu Y, Lindner J, Kumar A, Yuan W, Magnuson MA. Rictor/mTORC2 is essential for maintaining a balance between beta-cell proliferation and cell size. Diabetes  2011; 60(3): 827-37.
[http://dx.doi.org/10.2337/db10-1194] [PMID: 21266327] 
[310] 
Du LL, Chai DM, Zhao LN, et al. AMPK activation ameliorates Alzheimer’s disease-like pathology and spatial memory impairment in a streptozotocin-induced Alzheimer’s disease model in rats. J Alzheimers Dis  2015; 43(3): 775-84.
[http://dx.doi.org/10.3233/JAD-140564] [PMID: 25114075] 
[311] 
Jiang T, Yu JT, Zhu XC, et al. Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagy. Br J Pharmacol  2014; 171(13): 3146-57.
[http://dx.doi.org/10.1111/bph.12655] [PMID: 24611741] 
[312] 
Peixoto CA, de Oliveira WH, da Rocha Araujo SM, Nunes AKS. AMPK activation: Role in the signaling pathways of neuroinflammation and neurodegeneration. Exp Neurol  2017; 298(A): 31-41.
[313] 
Fulco M, Cen Y, Zhao P, et al. Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. Dev Cell  2008; 14(5): 661-73.
[http://dx.doi.org/10.1016/j.devcel.2008.02.004] [PMID: 18477450] 
[314] 
Nejabati HR, Samadi N, Shahnazi V, et al. Nicotinamide and its metabolite N1-Methylnicotinamide alleviate endocrine and metabolic abnormalities in adipose and ovarian tissues in rat model of Polycystic Ovary Syndrome. Chem Biol Interact  2020; 324: 109093.
[http://dx.doi.org/10.1016/j.cbi.2020.109093] [PMID: 32298659] 
[315] 
Stevens MJ, Li F, Drel VR, et al. Nicotinamide reverses neurological and neurovascular deficits in streptozotocin diabetic rats. J Pharmacol Exp Ther  2007; 320(1): 458-64.
[http://dx.doi.org/10.1124/jpet.106.109702] [PMID: 17021258] 
[316] 
Liu Y, Palanivel R, Rai E, et al. Adiponectin stimulates autophagy and reduces oxidative stress to enhance insulin sensitivity during high-fat diet feeding in mice. Diabetes  2015; 64(1): 36-48.
[http://dx.doi.org/10.2337/db14-0267] [PMID: 25071026] 
[317] 
Zhao H, Wang ZC, Wang KF, Chen XY. Aβ peptide secretion is reduced by Radix Polygalae-induced autophagy via activation of the AMPK/mTOR pathway. Mol Med Rep  2015; 12(2): 2771-6.
[http://dx.doi.org/10.3892/mmr.2015.3781] [PMID: 25976650] 
[318] 
Zhang ZH, Wu QY, Zheng R, et al. Selenomethionine mitigates cognitive decline by targeting both tau hyperphosphorylation and autophagic clearance in an Alzheimer’s disease mouse model. J Neurosci  2017; 37(9): 2449-62.
[http://dx.doi.org/10.1523/JNEUROSCI.3229-16.2017] [PMID: 28137967] 
[319] 
Yamashima T, Ota T, Mizukoshi E, et al. Intake of ω-6 Polyunsaturated Fatty Acid-Rich Vegetable Oils and Risk of Lifestyle Diseases. Adv Nutr  2020; 11(6): 1489-509.
[http://dx.doi.org/10.1093/advances/nmaa072] [PMID: 32623461] 
[320] 
Lee JH, Lee JH, Jin M, et al. Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats. Exp Mol Med  2014; 46: e111.
[http://dx.doi.org/10.1038/emm.2014.52] [PMID: 25168310] 
[321] 
Hu P, Lai D, Lu P, Gao J, He H. ERK and Akt signaling pathways are involved in advanced glycation end product-induced autophagy in rat vascular smooth muscle cells. Int J Mol Med  2012; 29(4): 613-8.
[http://dx.doi.org/10.3892/ijmm.2012.891] [PMID: 22293957] 
[322] 
Lee Y, Hong Y, Lee SR, Chang KT, Hong Y. Autophagy contributes to retardation of cardiac growth in diabetic rats. Lab Anim Res  2012; 28(2): 99-107.
[http://dx.doi.org/10.5625/lar.2012.28.2.99] [PMID: 22787483] 
Rights & Permissions Print Cite
Article Metrics
53
1
Journal Information
For Authors
For Editors
For Reviewers
Explore Articles
Open Access
Open Access Articles
For Visitors
DOI https://dx.doi.org/10.2174/1567202617999210104220334	Print ISSN 1567-2026
Publisher Name Bentham Science Publisher	Online ISSN 1875-5739
Current Neurovascular Research

Nicotinamide as a Foundation for Treating Neurodegenerative Disease and Metabolic Disorders

Abstract

Related Journals

Related Books

Related Articles
