AMPK and its Activator Berberine in the Treatment of Neurodegenerative Diseases

Author(s): Siru Qin, Huiling Tang, Wei Li, Yinan Gong, Shanshan Li, Jin Huang, Yuxin Fang, Wenjuan Yuan, Yangyang Liu, Shenjun Wang, Yongming Guo, Yi Guo*, Zhifang Xu*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 39 , 2020


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Abstract:

Neurodegenerative disorders are heterogeneous diseases associated with either acute or progressive neurodegeneration, causing the loss of neurons and axons in the central nervous system (CNS), showing high morbidity and mortality, and there are only a few effective therapies. Here, we summarized that the energy sensor adenosine 5‘-monophosphate (AMP)-activated protein kinase (AMPK), and its agonist berberine can combat the common underlying pathological events of neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial disorder, glutamate excitotoxicity, apoptosis, autophagy disorder, and disruption of neurovascular units. The abovementioned effects of berberine may primarily depend on activating AMPK and its downstream targets, such as the mammalian target of rapamycin (mTOR), sirtuin1 (SIRT1), nuclear factor erythroid-2 related factor-2 (Nrf2), nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), nicotinamide adenine dinucleotide (NAD+), and p38 mitogen-activated protein kinase (p38 MAPK). It is hoped that this review will provide a strong basis for further scientific exploration and development of berberine's therapeutic potential against neurodegeneration.

Keywords: Neurodegenerative diseases, AMPK, berberine, oxidative stress, mitochondrial disorder, glutamate excitotoxicity, neuroinflammation, apoptosis.

[1]
Amor S, Puentes F, Baker D, van der Valk P. Inflammation in neurodegenerative diseases. Immunology 2010; 129(2): 154-69.
[http://dx.doi.org/10.1111/j.1365-2567.2009.03225.x]] [PMID: 20561356]
[2]
Farooqui Akhlaq A. Neurochemical Aspects of Neurotraumatic and Neurodegenerative Diseases || Perspective and Direction for Future Developments on Neurotraumatic and Neurodegenerative Diseases. Springer New York 2010; pp. 383-97.
[http://dx.doi.org/10.1007/978-1-4419-6652-0_10.]
[3]
Mandel S, Grünblatt E, Riederer P, Gerlach M, Levites Y, Youdim MB. Neuroprotective strategies in Parkinson’s disease: an update on progress. CNS Drugs 2003; 17(10): 729-62.
[http://dx.doi.org/10.2165/00023210-200317100-00004] [PMID: 12873156]
[4]
Amato S, Man HY. Bioenergy sensing in the brain: the role of AMP-activated protein kinase in neuronal metabolism, development and neurological diseases. Cell Cycle 2011; 10(20): 3452-60.
[http://dx.doi.org/10.4161/cc.10.20.17953] [PMID: 22067656 ]
[5]
Stapleton D, Mitchelhill KI, Gao G, et al. Mammalian AMP-activated protein kinase subfamily. J Biol Chem 1996; 271(2): 611-4.
[http://dx.doi.org/10.1074/jbc.271.2.611] [PMID: 8557660]
[6]
Cotán D, Paz MV, Alcocer-Gómez E, et al. AMPK As A Target in Rare Diseases. Curr Drug Targets 2016; 17(8): 921-31.
[http://dx.doi.org/10.2174/1389450117666160112110204] [PMID: 26758671]
[7]
Marinangeli C, Didier S, Vingtdeux V. AMPK in neurodegenerative diseases: Implications and therapeutic perspectives. Curr Drug Targets 2016; 17(8): 890-907.
[http://dx.doi.org/10.2174/1389450117666160201105645] [PMID: 26073858]
[8]
Ahmed T, Gilani AU, Abdollahi M, Daglia M, Nabavi SF, Nabavi SM. Berberine and neurodegeneration: A review of literature. Pharmacol Rep 2015; 67(5): 970-9.
[http://dx.doi.org/10.1016/j.pharep.2015.03.002] [PMID: 26398393]
[9]
Wang K, Feng X, Chai L, Cao S, Qiu F. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metab Rev 2017; 49(2): 139-57.
[http://dx.doi.org/10.1080/03602532.2017.1306544] [PMID: 28290706]
[10]
Turner N, Li JY, Gosby A, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes 2008; 57(5): 1414-8.
[http://dx.doi.org/10.2337/db07-1552] [PMID: 18285556]
[11]
Amato S, Liu X, Zheng B, Cantley L, Rakic P, Man HY. AMP-activated protein kinase regulates neuronal polarization by interfering with PI 3-kinase localization. Science 2011; 332(6026): 247-51.
[http://dx.doi.org/10.1126/science.1201678] [PMID: 21436401]
[12]
Cantó C, Gerhart-Hines Z, Feige JN, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009; 458(7241): 1056-60.
[http://dx.doi.org/10.1038/nature07813] [PMID: 19262508]
[13]
Egan D, Kim J, Shaw RJ, Guan KL. The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR. Autophagy 2011; 7(6): 643-4.
[http://dx.doi.org/10.4161/auto.7.6.15123] [PMID: 21460621]
[14]
Ouchi N, Shibata R, Walsh K. AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle. Circ Res 2005; 96(8): 838-46.
[http://dx.doi.org/10.1161/01.RES.0000163633.10240.3b] [PMID: 15790954]
[15]
Salminen A, Hyttinen JM, Kaarniranta K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J Mol Med (Berl) 2011; 89(7): 667-76.
[http://dx.doi.org/10.1007/s00109-011-0748-0] [PMID: 21431325]
[16]
Zimmermann K, Baldinger J, Mayerhofer B, Atanasov AG, Dirsch VM, Heiss EH. Activated AMPK boosts the Nrf2/HO-1 signaling axis--A role for the unfolded protein response. Free Radic Biol Med 2015; 88(Pt B): 417-26.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.03.030] [PMID: 25843659 ]
[17]
Durairajan SS, Liu LF, Lu JH, et al. Berberine ameliorates β-amyloid pathology, gliosis, and cognitive impairment in an Alzheimer’s disease transgenic mouse model. Neurobiol Aging 2012; 33(12): 2903-19.
[http://dx.doi.org/10.1016/j.neurobiolaging.2012.02.016] [PMID: 22459600]
[18]
Giacoppo S, Galuppo M, Montaut S, et al. An overview on neuroprotective effects of isothiocyanates for the treatment of neurodegenerative diseases. Fitoterapia 2015; 106: 12-21.
[http://dx.doi.org/10.1016/j.fitote.2015.08.001] [PMID: 26254971]
[19]
Lee PC, Bordelon Y, Bronstein J, Ritz B. Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease. Neurology 2012; 79(20): 2061-6.
[http://dx.doi.org/10.1212/WNL.0b013e3182749f28] [PMID: 23150532]
[20]
Pluta R. From brain ischemia-reperfusion injury to possible sporadic Alzheimer’s disease. Curr Neurovasc Res 2004; 1(5): 441-53.
[http://dx.doi.org/10.2174/1567202043361839] [PMID: 16181092]
[21]
Oyinbo CA. Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Warsz) 2011; 71(2): 281-99.
[PMID: 21731081]
[22]
Saatman KE, Duhaime AC, Bullock R, Maas AI, Valadka A, Manley GT. Workshop Scientific Team and Advisory Panel Members. Classification of traumatic brain injury for targeted therapies. J Neurotrauma 2008; 25(7): 719-38.
[http://dx.doi.org/10.1089/neu.2008.0586] [PMID: 18627252]
[23]
Pundik S, Xu K, Sundararajan S. Reperfusion brain injury: focus on cellular bioenergetics. Neurology 2012; 79(13)(Suppl. 1): S44-51.
[http://dx.doi.org/10.1212/WNL.0b013e3182695a14] [PMID: 23008411]
[24]
Loane DJ, Faden AI. Neuroprotection for traumatic brain injury: translational challenges and emerging therapeutic strategies. Trends Pharmacol Sci 2010; 31(12): 596-604.
[http://dx.doi.org/10.1016/j.tips.2010.09.005] [PMID: 21035878]
[25]
Nagai Y, Fujikake N, Popiel HA, Wada K. Induction of molecular chaperones as a therapeutic strategy for the polyglutamine diseases. Curr Pharm Biotechnol 2010; 11(2): 188-97.
[http://dx.doi.org/10.2174/138920110790909650] [PMID: 20166962]
[26]
Kalia LV, Lang AE. Parkinson’s disease. Lancet 2015; 386(9996): 896-912.
[http://dx.doi.org/10.1016/S0140-6736(14)61393-3] [PMID: 25904081]
[27]
Aguilera G, Colín-González AL, Rangel-López E, Chavarría A, Santamaría A. Redox signaling, neuroinflammation, and neurodegeneration. Antioxid Redox Signal 2018; 28(18): 1626-51.
[http://dx.doi.org/10.1089/ars.2017.7099] [PMID: 28467722]
[28]
Grigoriadis N, van Pesch V, Paradig MS. Group. A basic overview of multiple sclerosis immunopathology. Eur J Neurol 2015; 22(Suppl. 2): 3-13.
[http://dx.doi.org/10.1111/ene.12798] [PMID: 26374508]
[29]
Liscic RM. Als and Ftd: Insights into the disease mechanisms and therapeutic targets. Eur J Pharmacol 2017; 817: 2-6.
[http://dx.doi.org/10.1016/j.ejphar.2017.10.012] [PMID: 29031901]
[30]
McColgan P, Tabrizi SJ. Huntington’s disease: a clinical review. Eur J Neurol 2018; 25(1): 24-34.
[http://dx.doi.org/10.1111/ene.13413] [PMID: 28817209]
[31]
Tarozzi A, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P. Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longev 2013.2013415078
[http://dx.doi.org/10.1155/2013/415078] [PMID: 23983898]
[32]
Li J, Zhong L, Wang F, Zhu H. Dissecting the role of AMP-activated protein kinase in human diseases. Acta Pharm Sin B 2017; 7(3): 249-59.
[http://dx.doi.org/10.1016/j.apsb.2016.12.003] [PMID: 28540163]
[33]
Xiao B, Sanders MJ, Underwood E, et al. Structure of mammalian AMPK and its regulation by ADP. Nature 2011; 472(7342): 230-3.
[http://dx.doi.org/10.1038/nature09932] [PMID: 21399626]
[34]
Marín-Aguilar F, Pavillard LE, Giampieri F, Bullón P, Cordero MD. Adenosine Monophosphate (AMP)-Activated protein kinase: A new target for nutraceutical compounds. Int J Mol Sci 2017; 18(2): 18.
[http://dx.doi.org/10.3390/ijms18020288] [PMID: 28146060]
[35]
Xu Z, Feng W, Shen Q, et al. Rhizoma coptidis and berberine as a natural drug to combat aging and aging-related diseases via Anti-oxidation and AMPK activation. Aging Dis 2017; 8(6): 760-77.
[http://dx.doi.org/10.14336/AD.2016.0620] [PMID: 29344415]
[36]
Greco SJ, Sarkar S, Johnston JM, Tezapsidis N. Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells. Biochem Biophys Res Commun 2009; 380(1): 98-104.
[http://dx.doi.org/10.1016/j.bbrc.2009.01.041] [PMID: 19166821]
[37]
Nath N, Khan M, Rattan R, et al. Loss of AMPK exacerbates experimental autoimmune encephalomyelitis disease severity. Biochem Biophys Res Commun 2009; 386(1): 16-20.
[http://dx.doi.org/10.1016/j.bbrc.2009.05.106] [PMID: 19486896]
[38]
Coughlan KS, Mitchem MR, Hogg MC, Prehn JH. “Preconditioning” with latrepirdine, an adenosine 5′-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiol Aging 2015; 36(2): 1140-50.
[http://dx.doi.org/10.1016/j.neurobiolaging.2014.09.022] [PMID: 25443289]
[39]
Curry DW, Stutz B, Andrews ZB, Elsworth JD. Targeting AMPK signaling as a neuroprotective strategy in Parkinson’s disease. J Parkinsons Dis 2018; 8(2): 161-81.
[http://dx.doi.org/10.3233/JPD-171296] [PMID: 29614701]
[40]
Jin J, Gu H, Anders NM, et al. Metformin protects cells from mutant huntingtin toxicity through activation of AMPK and modulation of mitochondrial dynamics. Neuromolecular Med 2016; 18(4): 581-92.
[http://dx.doi.org/10.1007/s12017-016-8412-z] [PMID: 27225841]
[41]
Sarkaki A, Farbood Y, Badavi M, Khalaj L, Khodagholi F, Ashabi G. Metformin improves anxiety-like behaviors through AMPK-dependent regulation of autophagy following transient forebrain ischemia. Metab Brain Dis 2015; 30(5): 1139-50.
[http://dx.doi.org/10.1007/s11011-015-9677-x] [PMID: 25936719]
[42]
Chang CF, Lee YC, Lee KH, et al. Therapeutic effect of berberine on TDP-43-related pathogenesis in FTLD and ALS. J Biomed Sci 2016; 23(1): 72.
[http://dx.doi.org/10.1186/s12929-016-0290-z] [PMID: 27769241]
[43]
Yin J, Zhang H, Ye J. Traditional chinese medicine in treatment of metabolic syndrome. Endocr Metab Immune Disord Drug Targets 2008; 8(2): 99-111.
[http://dx.doi.org/10.2174/187153008784534330] [PMID: 18537696]
[44]
Wang X, Wang R, Xing D, et al. Kinetic difference of berberine between hippocampus and plasma in rat after intravenous administration of Coptidis rhizoma extract. Life Sci 2005; 77(24): 3058-67.
[http://dx.doi.org/10.1016/j.lfs.2005.02.033] [PMID: 15996686]
[45]
Zhu F, Qian C. Berberine chloride can ameliorate the spatial memory impairment and increase the expression of interleukin-1beta and inducible nitric oxide synthase in the rat model of Alzheimer’s disease. BMC Neurosci 2006; 7: 78.
[http://dx.doi.org/10.1186/1471-2202-7-78] [PMID: 17137520]
[46]
Kim M, Cho KH, Shin MS, et al. Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson’s disease. Int J Mol Med 2014; 33(4): 870-8.
[http://dx.doi.org/10.3892/ijmm.2014.1656] [PMID: 24535622]
[47]
Wang Y, Zhou L, Li Y, et al. The effects of berberine on concanavalin A-Induced Autoimmune Hepatitis (AIH) in mice and the Adenosine 5′-Monophosphate (AMP)-Activated Protein Kinase (AMPK) pathway. Med Sci Monit 2017; 23: 6150-61.
[http://dx.doi.org/10.12659/MSM.907377] [PMID: 29283990]
[48]
Kunz A, Dirnagl U, Mergenthaler P. Acute pathophysiological processes after ischaemic and traumatic brain injury. Best Pract Res Clin Anaesthesiol 2010; 24(4): 495-509.
[http://dx.doi.org/10.1016/j.bpa.2010.10.001] [PMID: 21619862]
[49]
Metodiewa D, Kośka C. Reactive oxygen species and reactive nitrogen species: relevance to cyto(neuro)toxic events and neurologic disorders. An overview. Neurotox Res 2000; 1(3): 197-233.
[http://dx.doi.org/10.1007/BF03033290] [PMID: 12835102]
[50]
He L, He T, Farrar S, Ji L, Liu T, Ma X. Antioxidants maintain cellular redox homeostasis by elimination of reactive oxygen species. Cell Physiol Biochem 2017; 44(2): 532-53.
[http://dx.doi.org/10.1159/000485089] [PMID: 29145191]
[51]
Schmidley JW. Free radicals in central nervous system ischemia. Stroke 1990; 21(7): 1086-90.
[http://dx.doi.org/10.1161/01.STR.21.7.1086] [PMID: 2195717]
[52]
Bhat AH, Dar KB, Anees S, et al. Oxidative stress, mitochondrial dysfunction and neurodegenerative diseases; a mechanistic insight. Biomed Pharmacother 2015; 74: 101-10.
[http://dx.doi.org/10.1016/j.biopha.2015.07.025] [PMID: 26349970]
[53]
Tönnies E, Trushina E. Oxidative stress, synaptic dysfunction, and Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1105-21.
[http://dx.doi.org/10.3233/JAD-161088] [PMID: 28059794]
[54]
Huang SX, Qiu G, Cheng FR, et al. Berberine protects secondary injury in mice with traumatic brain injury through anti-oxidative and anti-inflammatory modulation. Neurochem Res 2018; 43(9): 1814-25.
[http://dx.doi.org/10.1007/s11064-018-2597-5] [PMID: 30027364]
[55]
Liu P, Zhao H, Wang R, et al. MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress. Stroke 2015; 46(2): 513-9.
[http://dx.doi.org/10.1161/STROKEAHA.114.007482] [PMID: 25523055]
[56]
Zhang Q, Fu X, Wang J, Yang M, Kong L. Treatment effects of ischemic stroke by berberine, baicalin, and jasminoidin from Huang-Lian-Jie-Du-Decoction (HLJDD) explored by an integrated metabolomics approach. Oxid Med Cell Longev 2017.20179848594
[http://dx.doi.org/10.1155/2017/9848594] [PMID: 28894512]
[57]
Crotty GF, Ascherio A, Schwarzschild MA. Targeting urate to reduce oxidative stress in Parkinson disease. Exp Neurol 2017; 298(Pt B): 210-4.
[http://dx.doi.org/10.1016/j.expneurol.2017.06.017] [PMID: 28622913]
[58]
Kumar A, Ratan RR. Oxidative stress and Huntington’s disease: The good, the bad, and the ugly. J Huntingtons Dis 2016; 5(3): 217-37.
[http://dx.doi.org/10.3233/JHD-160205] [PMID: 27662334]
[59]
Vomhof-Dekrey EE, Picklo MJ Sr. The Nrf2-antioxidant response element pathway: A target for regulating energy metabolism. J Nutr Biochem 2012; 23(10): 1201-6.
[http://dx.doi.org/10.1016/j.jnutbio.2012.03.005] [PMID: 22819548]
[60]
Motterlini R, Green CJ, Foresti R. Regulation of heme oxygenase-1 by redox signals involving nitric oxide. Antioxid Redox Signal 2002; 4(4): 615-24.
[http://dx.doi.org/10.1089/15230860260220111] [PMID: 12230873]
[61]
Cuadrado A, Rojo AI. Heme oxygenase-1 as a therapeutic target in neurodegenerative diseases and brain infections. Curr Pharm Des 2008; 14(5): 429-42.
[http://dx.doi.org/10.2174/138161208783597407] [PMID: 18289070]
[62]
Hwang YP, Jeong HG. The coffee diterpene kahweol induces heme oxygenase-1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6-hydroxydopamine-derived oxidative stress. FEBS Lett 2008; 582(17): 2655-62.
[http://dx.doi.org/10.1016/j.febslet.2008.06.045] [PMID: 18593583]
[63]
Hsu YY, Chen CS, Wu SN, Jong YJ, Lo YC. Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells. Eur J Pharm Sci 2012; 46(5): 415-25.
[http://dx.doi.org/10.1016/j.ejps.2012.03.004] [PMID: 22469516]
[64]
Bae J, Lee D, Kim YK, Gil M, Lee JY, Lee KJ. Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells 2013; 35(2): 151-7.
[http://dx.doi.org/10.1007/s10059-013-2298-5] [PMID: 23329300]
[65]
Russo MV, McGavern DB. Inflammatory neuroprotection following traumatic brain injury. Science 2016; 353(6301): 783-5.
[http://dx.doi.org/10.1126/science.aaf6260] [PMID: 27540166]
[66]
Kempuraj D, Thangavel R, Natteru PA, et al. Neuroinflammation induces neurodegeneration. J Neurol Neurosurg Spine 2016; 1(1): 1003.
[PMID: 28127589]
[67]
Qin X, Guo BT, Wan B, et al. Regulation of Th1 and Th17 cell differentiation and amelioration of experimental autoimmune encephalomyelitis by natural product compound berberine. J Immunol 2010; 185(3): 1855-63.
[http://dx.doi.org/10.4049/jimmunol.0903853] [PMID: 20622114]
[68]
Harry GJ, Lefebvre d’Hellencourt C, McPherson CA, Funk JA, Aoyama M, Wine RN. Tumor necrosis factor p55 and p75 receptors are involved in chemical-induced apoptosis of dentate granule neurons. J Neurochem 2008; 106(1): 281-98.
[http://dx.doi.org/10.1111/j.1471-4159.2008.05382.x] [PMID: 18373618]
[69]
Micheau O, Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003; 114(2): 181-90.
[http://dx.doi.org/10.1016/S0092-8674(03)00521-X] [PMID: 12887920]
[70]
Nitsch R, Bechmann I, Deisz RA, et al. Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Lancet 2000; 356(9232): 827-8.
[http://dx.doi.org/10.1016/S0140-6736(00)02659-3] [PMID: 11022932]
[71]
Bal-Price A, Brown GC. Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci 2001; 21(17): 6480-91.
[http://dx.doi.org/10.1523/JNEUROSCI.21-17-06480.2001] [PMID: 11517237]
[72]
He W, Wang C, Chen Y, He Y, Cai Z. Berberine attenuates cognitive impairment and ameliorates tau hyperphosphorylation by limiting the self-perpetuating pathogenic cycle between NF-κB signaling, oxidative stress and neuroinflammation. Pharmacol Rep 2017; 69(6): 1341-8.
[http://dx.doi.org/10.1016/j.pharep.2017.06.006] [PMID: 29132092]
[73]
Chen CC, Hung TH, Lee CY, et al. Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury. PLoS One 2014; 9(12)e115694
[http://dx.doi.org/10.1371/journal.pone.0115694] [PMID: 25546475]
[74]
Wang H, Liu C, Mei X, et al. Berberine attenuated pro-inflammatory factors and protect against neuronal damage via triggering oligodendrocyte autophagy in spinal cord injury. Oncotarget 2017; 8(58): 98312-21.
[http://dx.doi.org/10.18632/oncotarget.21203] [PMID: 29228691]
[75]
Zhu JR, Lu HD, Guo C, et al. Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation. Acta Pharmacol Sin 2018; 39(11): 1706-15.
[http://dx.doi.org/10.1038/s41401-018-0160-1] [PMID: 30266998]
[76]
Jia L, Liu J, Song Z, et al. Berberine suppresses amyloid-beta-induced inflammatory response in microglia by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase signalling pathways. J Pharm Pharmacol 2012; 64(10): 1510-21.
[http://dx.doi.org/10.1111/j.2042-7158.2012.01529.x] [PMID: 22943182]
[77]
Ma X, Jiang Y, Wu A, et al. Berberine attenuates experimental autoimmune encephalomyelitis in C57 BL/6 mice. PLoS One 2010; 5(10)e13489
[http://dx.doi.org/10.1371/journal.pone.0013489] [PMID: 20976070]
[78]
Golpich M, Amini E, Mohamed Z, Azman Ali R, Mohamed Ibrahim N, Ahmadiani A. Mitochondrial dysfunction and biogenesis in neurodegenerative diseases: pathogenesis and treatment. CNS Neurosci Ther 2017; 23(1): 5-22.
[http://dx.doi.org/10.1111/cns.12655] [PMID: 27873462]
[79]
Nakashima RA. Hexokinase-binding properties of the mitochondrial VDAC protein: inhibition by DCCD and location of putative DCCD-binding sites. J Bioenerg Biomembr 1989; 21(4): 461-70.
[http://dx.doi.org/10.1007/BF00762518] [PMID: 2478532]
[80]
Onyango IG, Lu J, Rodova M, Lezi E, Crafter AB, Swerdlow RH. Regulation of neuron mitochondrial biogenesis and relevance to brain health. Mitochondrial DysfunctionBiochimica et Biophysica Acta (BBA) -. Molecular Basis of Disease 2010; 1802: 228.
[http://dx.doi.org/10.1016/j.bbadis.2009.07.014] [PMID: 19682571]
[81]
Yonutas HM, Vekaria HJ, Sullivan PG. Mitochondrial specific therapeutic targets following brain injury Brain Res 2016; 1640(Pt A): 77-.
[http://dx.doi.org/10.1016/j.brainres.2016.02.007] [PMID: 26872596]
[82]
Filosto M, Scarpelli M, Cotelli MS, et al. The role of mitochondria in neurodegenerative diseases. J Neurol 2011; 258(10): 1763-74.
[http://dx.doi.org/10.1007/s00415-011-6104-z] [PMID: 21604203]
[83]
Cronin-Furman EN, Borland MK, Bergquist KE, Bennett JP Jr, Trimmer PA. Mitochondrial quality, dynamics and functional capacity in Parkinson’s disease cybrid cell lines selected for Lewy body expression. Mol Neurodegener 2013; 8: 6.
[http://dx.doi.org/10.1186/1750-1326-8-6] [PMID: 23351342]
[84]
Cantó C, Jiang LQ, Deshmukh AS, et al. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 2010; 11(3): 213-9.
[http://dx.doi.org/10.1016/j.cmet.2010.02.006] [PMID: 20197054]
[85]
Li L, Xiao L, Hou Y, et al. Sestrin2 silencing exacerbates cerebral ischemia/reperfusion injury by decreasing mitochondrial biogenesis through the AMPK/PGC-1α pathway in rats. Sci Rep 2016; 6: 30272.
[http://dx.doi.org/10.1038/srep30272] [PMID: 27453548]
[86]
Jäger S, Handschin C, St-Pierre J, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci USA 2007; 104(29): 12017-22.
[http://dx.doi.org/10.1073/pnas.0705070104] [PMID: 17609368]
[87]
Reznick RM, Shulman GI. The role of AMP-activated protein kinase in mitochondrial biogenesis. J Physiol 2006; 574(Pt 1): 33-9.
[http://dx.doi.org/10.1113/jphysiol.2006.109512] [PMID: 16709637]
[88]
Herskovits AZ, Guarente L. Sirtuin deacetylases in neurodegenerative diseases of aging. Cell Res 2013; 23(6): 746-58.
[http://dx.doi.org/10.1038/cr.2013.70] [PMID: 23689277]
[89]
Perera ND, Sheean RK, Scott JW, Kemp BE, Horne MK, Turner BJ. Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models. PLoS One 2014; 9(4)e95549
[http://dx.doi.org/10.1371/journal.pone.0095549] [PMID: 24740287]
[90]
Jiang M, Wang J, Fu J, et al. Neuroprotective role of Sirt1 in mammalian models of Huntington’s disease through activation of multiple Sirt1 targets. Nat Med 2011; 18(1): 153-8.
[http://dx.doi.org/10.1038/nm.2558] [PMID: 22179319]
[91]
Kim D, Nguyen MD, Dobbin MM, et al. SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 2007; 26(13): 3169-79.
[http://dx.doi.org/10.1038/sj.emboj.7601758] [PMID: 17581637]
[92]
Rivero-Segura NA, Flores-Soto E, García de la Cadena S, et al. Prolactin-induced neuroprotection against glutamate excitotoxicity is mediated by the reduction of [Ca2+]i overload and NF-κB activation. PLoS One 2017; 12(5)e0176910
[http://dx.doi.org/10.1371/journal.pone.0176910] [PMID: 28475602]
[93]
Meldrum BS. Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 2000; 130(4S)(Suppl.): 1007S-15S.
[http://dx.doi.org/10.1093/jn/130.4.1007S] [PMID: 10736372]
[94]
Dong XX, Wang Y, Qin ZH. Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin 2009; 30(4): 379-87.
[http://dx.doi.org/10.1038/aps.2009.24] [PMID: 19343058]
[95]
Choi DW. Ionic dependence of glutamate neurotoxicity. J Neurosci 1987; 7(2): 369-79.
[http://dx.doi.org/10.1523/JNEUROSCI.07-02-00369.1987] [PMID: 2880938]
[96]
Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science 2004; 305(5684): 626-9.
[http://dx.doi.org/10.1126/science.1099320] [PMID: 15286356]
[97]
Frankland PW, Bontempi B. The organization of recent and remote memories. Nat Rev Neurosci 2005; 6(2): 119-30.
[http://dx.doi.org/10.1038/nrn1607] [PMID: 15685217]
[98]
Newcomer JW, Farber NB, Olney JW. NMDA receptor function, memory, and brain aging. Dialogues Clin Neurosci 2000; 2(3): 219-32.
[PMID: 22034391]
[99]
Hsieh H, Boehm J, Sato C, et al. AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 2006; 52(5): 831-43.
[http://dx.doi.org/10.1016/j.neuron.2006.10.035] [PMID: 17145504]
[100]
Snyder EM, Nong Y, Almeida CG, et al. Regulation of NMDA receptor trafficking by amyloid-beta. Nat Neurosci 2005; 8(8): 1051-8.
[http://dx.doi.org/10.1038/nn1503] [PMID: 16025111]
[101]
Bezprozvanny I, Mattson MP. Neuronal calcium mishandling and the pathogenesis of Alzheimer’s disease. Trends Neurosci 2008; 31(9): 454-63.
[http://dx.doi.org/10.1016/j.tins.2008.06.005] [PMID: 18675468]
[102]
Ambrosi G, Cerri S, Blandini F. A further update on the role of excitotoxicity in the pathogenesis of Parkinson’s disease. J Neural Transm (Vienna) 2014; 121(8): 849-59.
[http://dx.doi.org/10.1007/s00702-013-1149-z] [PMID: 24380931]
[103]
Del Río P, Montiel T, Chagoya V, Massieu L. Exacerbation of excitotoxic neuronal death induced during mitochondrial inhibition in vivo: relation to energy imbalance or ATP depletion? Neuroscience 2007; 146(4): 1561-70.
[http://dx.doi.org/10.1016/j.neuroscience.2007.03.024] [PMID: 17490821]
[104]
Mrsić-Pelcić J, Pelcić G, Vitezić D, et al. Hyperbaric oxygen treatment: The influence on the hippocampal superoxide dismutase and Na+,K+-ATPase activities in global cerebral ischemia-exposed rats. Neurochem Int 2004; 44(8): 585-94.
[http://dx.doi.org/10.1016/j.neuint.2003.10.004] [PMID: 15016473]
[105]
Ikematsu N, Dallas ML, Ross FA, et al. Phosphorylation of the voltage-gated potassium channel Kv2.1 by AMP-activated protein kinase regulates membrane excitability. Proc Natl Acad Sci USA 2011; 108(44): 18132-7.
[http://dx.doi.org/10.1073/pnas.1106201108] [PMID: 22006306]
[106]
Culmsee C, Monnig J, Kemp BE, Mattson MP. AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation. J Mol Neurosci 2001; 17(1): 45-58.
[http://dx.doi.org/10.1385/JMN:17:1:45] [PMID: 11665862]
[107]
Wang P, Xu TY, Guan YF, et al. Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol 2011; 69(2): 360-74.
[http://dx.doi.org/10.1002/ana.22236] [PMID: 21246601]
[108]
Ascher P, Nowak L. A patch-clamp study of excitatory amino acid activated channels. Adv Exp Med Biol 1986; 203: 507-11.
[http://dx.doi.org/10.1007/978-1-4684-7971-3_39] [PMID: 2431603]
[109]
Budd SL, Nicholls DG. Mitochondria, calcium regulation, and acute glutamate excitotoxicity in cultured cerebellar granule cells. J Neurochem 1996; 67(6): 2282-91.
[http://dx.doi.org/10.1046/j.1471-4159.1996.67062282.x] [PMID: 8931459]
[110]
Weisová P, Alvarez SP, Kilbride SM, et al. Latrepirdine is a potent activator of AMP-activated protein kinase and reduces neuronal excitability Transl Psychiatry 2013; 3e317
[http://dx.doi.org/10.1038/tp.2013.92] [PMID: 24150226]
[111]
Nadjafi S, Ebrahimi SA, Rahbar-Roshandel N. Protective effects of berberine on oxygen-glucose deprivation/reperfusion on oligodendrocyte cell line (OLN-93). Int J Prev Med 2014; 5(9): 1153-60.
[PMID: 25317299]
[112]
Stoica BA, Faden AI. Cell death mechanisms and modulation in traumatic brain injury. Neurotherapeutics 2010; 7(1): 3-12.
[http://dx.doi.org/10.1016/j.nurt.2009.10.023] [PMID: 20129492]
[113]
Zhang X, Chen Y, Jenkins LW, Kochanek PM, Clark RS. Bench-to-bedside review: Apoptosis/programmed cell death triggered by traumatic brain injury. Crit Care 2005; 9(1): 66-75.
[http://dx.doi.org/10.1186/cc2950] [PMID: 15693986]
[114]
Cohen GM. Caspases: the executioners of apoptosis. Biochem J 1997; 326(Pt 1): 1-16.
[http://dx.doi.org/10.1042/bj3260001] [PMID: 9337844]
[115]
Oltvai ZN, Milliman CL, Korsmeyer SJ. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell 1993; 74(4): 609-19.
[http://dx.doi.org/10.1016/0092-8674(93)90509-O] [PMID: 8358790]
[116]
Ahmad K, Balaramnavar VM, Baig MH, Srivastava AK, Khan S, Kamal MA. Identification of potent caspase-3 inhibitors for treatment of multi- neurodegenerative diseases using pharmacophore modeling and docking approaches. CNS Neurol Disord Drug Targets 2014; 13(8): 1346-53.
[http://dx.doi.org/10.2174/1871527313666141023120843] [PMID: 25345515]
[117]
Cartier J, Marivin A, Berthelet J, Dubrez L. IAPs: a central element in the NF-κB activating signaling pathway. Med Sci (Paris) 2012; 28(1): 69-75.
[http://dx.doi.org/10.1051/medsci/2012281019] [PMID: 22289833]
[118]
Namura S, Zhu J, Fink K, et al. Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci 1998; 18(10): 3659-68.
[http://dx.doi.org/10.1523/JNEUROSCI.18-10-03659.1998] [PMID: 9570797]
[119]
Pollack M, Phaneuf S, Dirks A, Leeuwenburgh C. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann N Y Acad Sci 2002; 959: 93-107.
[http://dx.doi.org/10.1111/j.1749-6632.2002.tb02086.x] [PMID: 11976189]
[120]
Zhang MH, Zhou XM, Cui JZ, Wang KJ, Feng Y, Zhang HA. Neuroprotective effects of dexmedetomidine on traumatic brain injury: Involvement of neuronal apoptosis and HSP70 expression. Mol Med Rep 2018; 17(6): 8079-86.
[http://dx.doi.org/10.3892/mmr.2018.8898] [PMID: 29693126]
[121]
Liang Y, Huang M, Jiang X, Liu Q, Chang X, Guo Y. The neuroprotective effects of Berberine against amyloid β-protein-induced apoptosis in primary cultured hippocampal neurons via mitochondria-related caspase pathway. Neurosci Lett 2017; 655: 46-53.
[http://dx.doi.org/10.1016/j.neulet.2017.06.048] [PMID: 28668383]
[122]
Kim M, Shin MS, Lee JM, et al. Inhibitory Effects of isoquinoline alkaloid berberine on ischemia-induced apoptosis via activation of phosphoinositide 3-kinase/protein kinase b signaling pathway. Int Neurourol J 2014; 18(3): 115-25.
[http://dx.doi.org/10.5213/inj.2014.18.3.115] [PMID: 25279238]
[123]
Baba T, Kameda M, Yasuhara T, et al. Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/Akt signaling pathway. Stroke 2009; 40(11): e598-605.
[http://dx.doi.org/10.1161/STROKEAHA.109.563627] [PMID: 19762690]
[124]
Simões Pires EN, Frozza RL, Hoppe JB, Menezes Bde M, Salbego CG. Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved. Brain Res 2014; 1557: 26-33.
[http://dx.doi.org/10.1016/j.brainres.2014.02.021] [PMID: 24560603]
[125]
Zhang C, Li C, Chen S, et al. Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways. Redox Biol 2017; 11: 1-11.
[http://dx.doi.org/10.1016/j.redox.2016.10.019] [PMID: 27835779]
[126]
Jiang S, Li T, Ji T, et al. AMPK: Potential therapeutic target for ischemic stroke. Theranostics 2018; 8(16): 4535-51.
[http://dx.doi.org/10.7150/thno.25674] [PMID: 30214637]
[127]
Tian F, Deguchi K, Yamashita T, et al. In vivo imaging of autophagy in a mouse stroke model. Autophagy 2010; 6(8): 1107-14.
[http://dx.doi.org/10.4161/auto.6.8.13427] [PMID: 20930570]
[128]
Hara T, Nakamura K, Matsui M, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 2006; 441(7095): 885-9.
[http://dx.doi.org/10.1038/nature04724] [PMID: 16625204]
[129]
Komatsu M, Waguri S, Chiba T, et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006; 441(7095): 880-4.
[http://dx.doi.org/10.1038/nature04723] [PMID: 16625205]
[130]
Ott M, Gogvadze V, Orrenius S, Zhivotovsky B. Mitochondria, oxidative stress and cell death. Apoptosis 2007; 12(5): 913-22.
[http://dx.doi.org/10.1007/s10495-007-0756-2] [PMID: 17453160]
[131]
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]
[132]
Sekiguchi A, Kanno H, Ozawa H, Yamaya S, Itoi E. Rapamycin promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury in mice. J Neurotrauma 2012; 29(5): 946-56.
[http://dx.doi.org/10.1089/neu.2011.1919] [PMID: 21806471]
[133]
Din FV, Valanciute A, Houde VP, et al. Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells. Gastroenterology 2012; 142(7): 1504-15.e3.
[http://dx.doi.org/10.1053/j.gastro.2012.02.050] [PMID: 22406476]
[134]
Saiki S, Sasazawa Y, Imamichi Y, et al. Caffeine induces apoptosis by enhancement of autophagy via PI3K/Akt/mTOR/p70S6K inhibition. Autophagy 2011; 7(2): 176-87.
[http://dx.doi.org/10.4161/auto.7.2.14074] [PMID: 21081844]
[135]
Liu Y, Lu Z, Cui M, Yang Q, Tang Y, Dong Q. Tissue kallikrein protects SH-SY5Y neuronal cells against oxygen and glucose deprivation-induced injury through bradykinin B2 receptor-dependent regulation of autophagy induction. J Neurochem 2016; 139(2): 208-20.
[http://dx.doi.org/10.1111/jnc.13690] [PMID: 27248356]
[136]
Guo W, Qian L, Zhang J, et al. Sirt1 overexpression in neurons promotes neurite outgrowth and cell survival through inhibition of the mTOR signaling. J Neurosci Res 2011; 89(11): 1723-36.
[http://dx.doi.org/10.1002/jnr.22725] [PMID: 21826702]
[137]
Chau MD, Gao J, Yang Q, Wu Z, Gromada J. Fibroblast growth factor 21 regulates energy metabolism by activating the AMPK-SIRT1-PGC-1alpha pathway. Proc Natl Acad Sci USA 2010; 107(28): 12553-8.
[http://dx.doi.org/10.1073/pnas.1006962107] [PMID: 20616029]
[138]
Wu Y, Li X, Zhu JX, et al. Resveratrol-activated AMPK/SIRT1/autophagy in cellular models of Parkinson’s disease. Neurosignals 2011; 19(3): 163-74.
[http://dx.doi.org/10.1159/000328516] [PMID: 21778691]
[139]
Muoio V, Persson PB, Sendeski MM. The neurovascular unit - concept review. Acta Physiol (Oxf) 2014; 210(4): 790-8.
[http://dx.doi.org/10.1111/apha.12250] [PMID: 24629161]
[140]
Sweeney MD, Ayyadurai S, Zlokovic BV. Pericytes of the neurovascular unit: Key functions and signaling pathways. Nat Neurosci 2016; 19(6): 771-83.
[http://dx.doi.org/10.1038/nn.4288] [PMID: 27227366]
[141]
Abdul-Muneer PM, Chandra N, Haorah J. Interactions of oxidative stress and neurovascular inflammation in the pathogenesis of traumatic brain injury. Mol Neurobiol 2015; 51(3): 966-79.
[http://dx.doi.org/10.1007/s12035-014-8752-3] [PMID: 24865512]
[142]
Wu C, Chen J, Chen C, et al. Wnt/β-catenin coupled with HIF-1α/VEGF signaling pathways involved in galangin neurovascular unit protection from focal cerebral ischemia. Sci Rep 2015; 5: 16151.
[http://dx.doi.org/10.1038/srep16151] [PMID: 26537366]
[143]
Melincovici CS, Boşca AB, Şuşman S, et al. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol 2018; 59(2): 455-67.
[PMID: 30173249]
[144]
Lange C, Storkebaum E, de Almodóvar CR, Dewerchin M, Carmeliet P. Vascular endothelial growth factor: a neurovascular target in neurological diseases. Nat Rev Neurol 2016; 12(8): 439-54.
[http://dx.doi.org/10.1038/nrneurol.2016.88] [PMID: 27364743]
[145]
Salehi A, Zhang JH, Obenaus A. Response of the cerebral vasculature following traumatic brain injury. J Cereb Blood Flow Metab 2017; 37(7): 2320-39.
[http://dx.doi.org/10.1177/0271678X17701460] [PMID: 28378621]
[146]
Ruiz de Almodovar C, Lambrechts D, Mazzone M, Carmeliet P. Role and therapeutic potential of VEGF in the nervous system. Physiol Rev 2009; 89(2): 607-48.
[http://dx.doi.org/10.1152/physrev.00031.2008] [PMID: 19342615]
[147]
Zou J, Chen Z, Wei X, et al. Cystatin C as a potential therapeutic mediator against Parkinson’s disease via VEGF-induced angiogenesis and enhanced neuronal autophagy in neurovascular units. Cell Death Dis 2017; 8(6)e2854
[http://dx.doi.org/10.1038/cddis.2017.240] [PMID: 28569795]
[148]
Yang SP, Bae DG, Kang HJ, Gwag BJ, Gho YS, Chae CB. Co-accumulation of vascular endothelial growth factor with beta-amyloid in the brain of patients with Alzheimer’s disease. Neurobiol Aging 2004; 25(3): 283-90.
[http://dx.doi.org/10.1016/S0197-4580(03)00111-8] [PMID: 15123332]
[149]
Keifer OP Jr, O’Connor DM, Boulis NM. Gene and protein therapies utilizing VEGF for ALS. Pharmacol Ther 2014; 141(3): 261-71.
[http://dx.doi.org/10.1016/j.pharmthera.2013.10.009] [PMID: 24177067]
[150]
Salt IP, Hardie DG. AMP-Activated Protein Kinase: An ubiquitous signaling pathway with key roles in the cardiovascular system. Circ Res 2017; 120(11): 1825-41.
[http://dx.doi.org/10.1161/CIRCRESAHA.117.309633] [PMID: 28546359]
[151]
Frati A, Cerretani D, Fiaschi AI, et al. Diffuse axonal injury and oxidative stress: A comprehensive review. Int J Mol Sci 2017; 18(12): 18.
[http://dx.doi.org/10.3390/ijms18122600] [PMID: 29207487]
[152]
Wang HC, Wang BD, Chen MS, et al. Neuroprotective effect of berberine against learning and memory deficits in diffuse axonal injury. Exp Ther Med 2018; 15(1): 1129-35.
[PMID: 29399112]


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