Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Cross-Interplay between Osmolytes and mTOR in Alzheimer's Disease Pathogenesis

Author(s): Zeba Mueed, Devanshu Mehta, Pankaj K. Rai, Mohammad A. Kamal and Nitesh K. Poddar*

Volume 26 , Issue 37 , 2020

Page: [4699 - 4711] Pages: 13

DOI: 10.2174/1381612826666200518112355

Price: $65

Abstract

Alzheimer’s disease, categorized by the piling of amyloid-β (Aβ), hyperphosphorylated tau, PHFs, NFTs and mTOR hyperactivity, is a neurodegenerative disorder, affecting people across the globe. Osmolytes are known for osmoprotectants and play a pivotal role in protein folding, function and protein stability, thus, preventing proteins aggregation, and counteracting effects of denaturing solutes on proteins. Osmolytes (viz., sorbitol, inositol, and betaine) perform a pivotal function of maintaining homeostasis during hyperosmotic stress. The selective advantage of utilising osmolytes over inorganic ions by cells is in maintaining cell volume without compromising cell function, which is important for organs such as the brain. Osmolytes have been documented not only as neuroprotectors but they also seem to act as neurodegenerators. Betaine, sucrose and trehalose supplementation has been seen to induce autophagy thereby inhibiting the accumulation of Aβ. In contrast, sucrose has also been associated with mTOR hyperactivity, a hallmark of AD pathology. The neuroprotective action of taurine is revealed when taurine supplementation is seen to inhibit neural damage, apoptosis and oxidative damage. Inositol stereoisomers (viz., scyllo-inositol and myo-inositol) have also been seen to inhibit Aβ production and plaque formation in the brain, inhibiting AD pathogenesis. However, TMAO affects the aging process adversely by deregulating the mTOR signalling pathway and then kindling cognitive dysfunction via degradation of chemical synapses and synaptic plasticity. Thus, it can be concluded that osmolytes may act as a probable therapeutic approach for neurodevelopmental disorders. Here, we have reviewed and focussed upon the impact of osmolytes on mTOR signalling pathway and thereby its role in AD pathogenesis.

Keywords: Hyperosmotic stress, osmolytes, mTOR, , tau, autophagy.

[1]
Wang J, Gu BJ, Masters CL, Wang YJ. A systemic view of Alzheimer disease - insights from amyloid-β metabolism beyond the brain. Nat Rev Neurol 2017; 13(11): 703.
[http://dx.doi.org/10.1038/nrneurol.2017.147 ] [PMID: 29027541]
[2]
Galvan V, Hart MJ. Vascular mTOR-dependent mechanisms linking the control of aging to Alzheimer’s disease. Biochim Biophys Acta 2016; 1862(5): 992-1007.
[http://dx.doi.org/10.1016/j.bbadis.2015.11.010 ] [PMID: 26639036]
[3]
Hahr JY. Physiology of the Alzheimer’s disease. Med Hypotheses 2015; 85(6): 944-6.
[http://dx.doi.org/10.1016/j.mehy.2015.09.005 ] [PMID: 26386488]
[4]
Crews L, Masliah E. Molecular mechanisms of neurodegeneration in Alzheimer’s disease. Hum Mol Genet 2010; 19(R1): R12-20.
[http://dx.doi.org/10.1093/hmg/ddq160 ] [PMID: 20413653]
[5]
Mueed Z, Tandon P, Maurya SK, Deval R, Kamal MA, Poddar NK. Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer’s Development. Front Neurosci 2019; 12: 1017.
[http://dx.doi.org/10.3389/fnins.2018.01017 ] [PMID: 30686983]
[6]
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers 2015; 1: 15056.
[http://dx.doi.org/10.1038/nrdp.2015.56 ] [PMID: 27188934]
[7]
Mattson MP. Pathways towards and away from Alzheimer’s disease. Nature 2004; 430(7000): 631-9.
[http://dx.doi.org/10.1038/nature02621 ] [PMID: 15295589]
[8]
Stoothoff WH, Johnson GV. Hyperosmotic stress-induced apoptosis and tau phosphorylation in human neuroblastoma cells. J Neurosci Res 2001; 65(6): 573-82.
[http://dx.doi.org/10.1002/jnr.1187 ] [PMID: 11550225]
[9]
Sotiropoulos I, Catania C, Pinto LG, et al. Stress acts cumulatively to precipitate Alzheimer’s disease-like tau pathology and cognitive deficits. J Neurosci 2011; 31(21): 7840-7.
[http://dx.doi.org/10.1523/JNEUROSCI.0730-11.2011 ] [PMID: 21613497]
[10]
Dafre AL, Schmitz AE, Maher P. Hyperosmotic Stress Initiates AMPK-Independent Autophagy and AMPK- and Autophagy-Independent Depletion of Thioredoxin 1 and Glyoxalase 2 in HT22 Nerve Cells. Oxid Med Cell Longev 2019.20192715810
[http://dx.doi.org/10.1155/2019/2715810 ] [PMID: 31049129]
[11]
Ham DJ, Lynch GS, Koopman R. Amino acid sensing and activation of mechanistic target of rapamycin complex 1: implications for skeletal muscle. Curr Opin Clin Nutr Metab Care 2016; 19(1): 67-73.
[http://dx.doi.org/10.1097/MCO.0000000000000240 ] [PMID: 26560525]
[12]
Yan L, Lamb RF. Amino acid sensing and regulation of mTORC1. Semin Cell Dev Biol 2012; 23(6): 621-5.
[http://dx.doi.org/10.1016/j.semcdb.2012.02.001 ] [PMID: 22342805]
[13]
Burg MB, Ferraris JD. Intracellular organic osmolytes: function and regulation. J Biol Chem 2008; 283(12): 7309-13.
[http://dx.doi.org/10.1074/jbc.R700042200 ] [PMID: 18256030]
[14]
Jamal S, Poddar NK, Singh LR, Dar TA, Rishi V, Ahmad F. Relationship between functional activity and protein stability in the presence of all classes of stabilizing osmolytes. FEBS J 2009; 276(20): 6024-32.
[http://dx.doi.org/10.1111/j.1742-4658.2009.07317.x ] [PMID: 19765077]
[15]
Watanabe K, Umeda T, Niwa K, Naguro I, Ichijo H A. PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress. Cell Rep 2018; 22(11): 2809-17.
[http://dx.doi.org/10.1016/j.celrep.2018.02.045 ] [PMID: 29539411]
[16]
Schliess F, Richter L, vom Dahl S, Häussinger D. Cell hydration and mTOR-dependent signalling. Acta Physiol (Oxf) 2006; 187(1-2): 223-9.
[http://dx.doi.org/10.1111/j.1748-1716.2006.01547.x ] [PMID: 16734759]
[17]
Sørensen BH, Thorsteinsdottir UA, Lambert IH. Acquired cisplatin resistance in human ovarian A2780 cancer cells correlates with shift in taurine homeostasis and ability to volume regulate. Am J Physiol Cell Physiol 2014; 307(12): C1071-80.
[http://dx.doi.org/10.1152/ajpcell.00274.2014 ] [PMID: 25252947]
[18]
Jhanwar-Uniyal M, Gillick JL, Neil J, Tobias M, Thwing ZE, Murali R. Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: a tale of two complexes. Adv Biol Regul 2015; 57: 64-74.
[http://dx.doi.org/10.1016/j.jbior.2014.09.004 ] [PMID: 25442674]
[19]
Choi J, Chen J, Schreiber SL, Clardy J. Structure of the FKBP12-rapamycin complex interacting with the binding domain of human FRAP. Science 1996; 273(5272): 239-42.
[http://dx.doi.org/10.1126/science.273.5272.239 ] [PMID: 8662507]
[20]
Suryawan A, Jeyapalan AS, Orellana RA, Wilson FA, Nguyen HV, Davis TA. Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation. Am J Physiol Endocrinol Metab 2008; 295(4): E868-75.
[http://dx.doi.org/10.1152/ajpendo.90314.2008 ] [PMID: 18682538]
[21]
Fumarola C, La Monica S, Guidotti GG. Amino acid signaling through the mammalian target of rapamycin (mTOR) pathway: Role of glutamine and of cell shrinkage. J Cell Physiol 2005; 204(1): 155-65.
[http://dx.doi.org/10.1002/jcp.20272 ] [PMID: 15605414]
[22]
Yao Y, Jones E, Inoki K. Lysosomal Regulation of mTORC1 by Amino Acids in Mammalian Cells. Biomolecules 2017; 7(3)E51
[http://dx.doi.org/10.3390/biom7030051 ] [PMID: 28686218]
[23]
Wolfson RL, Chantranupong L, Saxton RA, et al. Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 2016; 351(6268): 43-8.
[http://dx.doi.org/10.1126/science.aab2674 ] [PMID: 26449471]
[24]
Li H, Ye D, Xie W, et al. Defect of branched-chain amino acid metabolism promotes the development of Alzheimer’s disease by targeting the mTOR signaling. Biosci Rep 2018; 38(4)BSR20180127
[http://dx.doi.org/10.1042/BSR20180127 ] [PMID: 29802157]
[25]
Tsun ZY, Bar-Peled L, Chantranupong L, et al. The folliculin tumor suppressor is a GAP for the RagC/D GTPases that signal amino acid levels to mTORC1. Mol Cell 2013; 52(4): 495-505.
[http://dx.doi.org/10.1016/j.molcel.2013.09.016 ] [PMID: 24095279]
[26]
Yoon MS, Son K, Arauz E, Han JM, Kim S, Chen J. Leucyl-tRNA Synthetase Activates Vps34 in Amino Acid-Sensing mTORC1 Signaling. Cell Rep 2016; 16(6): 1510-7.
[http://dx.doi.org/10.1016/j.celrep.2016.07.008 ] [PMID: 27477288]
[27]
Wang S, Tsun ZY, Wolfson RL, et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 2015; 347(6218): 188-94.
[http://dx.doi.org/10.1126/science.1257132 ] [PMID: 25567906]
[28]
Griffin JWD, Bradshaw PC. Amino Acid Catabolism in Alzheimer’s Disease Brain: Friend or Foe? Oxid Med Cell Longev 2017; 2017: 5472792-2.
[http://dx.doi.org/10.1155/2017/5472792 ] [PMID: 28261376]
[29]
Carroll B, Maetzel D, Maddocks OD, et al. Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife 2016; 5: 5.
[http://dx.doi.org/10.7554/eLife.11058 ] [PMID: 26742086]
[30]
Talboom JS, Velazquez R, Oddo S. The mammalian target of rapamycin at the crossroad between cognitive aging and Alzheimer’s disease. NPJ Aging Mech Dis 2015; 1: 15008.
[http://dx.doi.org/10.1038/npjamd.2015.8 ] [PMID: 28721257]
[31]
Nicklin P, Bergman P, Zhang B, et al. Bidirectional transport of amino acids regulates mTOR and autophagy. Cell 2009; 136(3): 521-34.
[http://dx.doi.org/10.1016/j.cell.2008.11.044 ] [PMID: 19203585]
[32]
Park E, Park SY, Dobkin C, Schuller-Levis G. Development of a novel cysteine sulfinic Acid decarboxylase knockout mouse: dietary taurine reduces neonatal mortality. J Amino Acids 2014.2014346809
[http://dx.doi.org/10.1155/2014/346809 ] [PMID: 24639894]
[33]
Jakaria M, Azam S, Haque ME, et al. Taurine and its analogs in neurological disorders: Focus on therapeutic potential and molecular mechanisms. Redox Biol 2019.24101223
[http://dx.doi.org/10.1016/j.redox.2019.101223 ] [PMID: 31141786]
[34]
Abdel-Moneim AM, Al-Kahtani MA, El-Kersh MA, Al-Omair MA. Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage. PLoS One 2015; 10(12): e0144509.
[http://dx.doi.org/10.1371/journal.pone.0144509 ] [PMID: 26659465]
[35]
Ashkani-Esfahani S, Zarifi F, Asgari Q, Samadnejad AZ, Rafiee S, Noorafshan A. Taurine improves the wound healing process in cutaneous leishmaniasis in mice model, based on stereological parameters. Adv Biomed Res 2014; 3: 204.
[http://dx.doi.org/10.4103/2277-9175.142314 ] [PMID: 25337534]
[36]
Miyamoto TA, Ueno T, Iguro Y, et al. Taurine-mediated cardioprotection is greater when administered upon reperfusion than prior to ischemia. Adv Exp Med Biol 2009; 643: 27-36.
[http://dx.doi.org/10.1007/978-0-387-75681-3_3 ] [PMID: 19239133]
[37]
Sirdah MM. Protective and therapeutic effectiveness of taurine in diabetes mellitus: a rationale for antioxidant supplementation. Diabetes Metab Syndr 2015; 9(1): 55-64.
[http://dx.doi.org/10.1016/j.dsx.2014.05.001 ] [PMID: 25366895]
[38]
Heidari R, Jamshidzadeh A, Niknahad H, et al. Effect of taurine on chronic and acute liver injury: Focus on blood and brain ammonia. Toxicol Rep 2016; 3: 870-9.
[http://dx.doi.org/10.1016/j.toxrep.2016.04.002 ] [PMID: 28959615]
[39]
Terrill JR, Pinniger GJ, Graves JA, Grounds MD, Arthur PG. Increasing taurine intake and taurine synthesis improves skeletal muscle function in the mdx mouse model for Duchenne muscular dystrophy. J Physiol 2016; 594(11): 3095-110.
[http://dx.doi.org/10.1113/JP271418 ] [PMID: 26659826]
[40]
Ahmadian M, Roshan VD, Aslani E, Stannard SR. Taurine supplementation has anti-atherogenic and anti-inflammatory effects before and after incremental exercise in heart failure. Ther Adv Cardiovasc Dis 2017; 11(7): 185-94.
[http://dx.doi.org/10.1177/1753944717711138 ] [PMID: 28580833]
[41]
Jang H, Lee S, Choi SL, Kim HY, Baek S, Kim Y. Taurine Directly Binds to Oligomeric Amyloid-β and Recovers Cognitive Deficits in Alzheimer Model Mice. Adv Exp Med Biol 2017; 975(Pt 1): 233-41.
[http://dx.doi.org/10.1007/978-94-024-1079-2_21 ] [PMID: 28849459]
[42]
Che Y, Hou L, Sun F, et al. Taurine protects dopaminergic neurons in a mouse Parkinson’s disease model through inhibition of microglial M1 polarization. Cell Death Dis 2018; 9(4): 435.
[http://dx.doi.org/10.1038/s41419-018-0468-2 ] [PMID: 29568078]
[43]
Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HM. Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington’s disease phenotype. Pharmacol Biochem Behav 2005; 82(3): 574-82.
[http://dx.doi.org/10.1016/j.pbb.2005.10.018 ] [PMID: 16337998]
[44]
Das J, Ghosh J, Manna P, Sinha M, Sil PC. Taurine protects rat testes against NaAsO(2)-induced oxidative stress and apoptosis via mitochondrial dependent and independent pathways. Toxicol Lett 2009; 187(3): 201-10.
[http://dx.doi.org/10.1016/j.toxlet.2009.03.001 ] [PMID: 19429265]
[45]
Zhang B, Yang X, Gao X. Taurine protects against bilirubininduced neurotoxicity in vitro. Brain Res 2010; 1320: 159-67.
[http://dx.doi.org/10.1016/j.brainres.2010.01.036 ] [PMID: 20096270]
[46]
Zhou J, Li Y, Yan G, et al. Protective role of taurine against morphine-induced neurotoxicity in C6 cells via inhibition of oxidative stress. Neurotox Res 2011; 20(4): 334-42.
[http://dx.doi.org/10.1007/s12640-011-9247-x ] [PMID: 21611853]
[47]
Shao X, Hu Z, Hu C, et al. Taurine protects methamphetamineinduced developmental angiogenesis defect through antioxidant mechanism. Toxicol Appl Pharmacol 2012; 260(3): 260-70.
[http://dx.doi.org/10.1016/j.taap.2012.03.003 ] [PMID: 22426360]
[48]
Nopparat C, Porter JE, Ebadi M, Govitrapong P. The mechanism for the neuroprotective effect of melatonin against methamphetamine-induced autophagy. J Pineal Res 2010; 49(4): 382-9.
[http://dx.doi.org/10.1111/j.1600-079X.2010.00805.x ] [PMID: 20738755]
[49]
Alers S, Löffler AS, Wesselborg S, Stork B. Role of AMPKmTOR-Ulk1/2 in the regulation of autophagy: cross talk, shortcuts, and feedbacks. Mol Cell Biol 2012; 32(1): 2-11.
[http://dx.doi.org/10.1128/MCB.06159-11 ] [PMID: 22025673]
[50]
de Melo AC, Paulino E, Garces AH. A Review of mTOR Pathway Inhibitors in Gynecologic Cancer. Oxid Med Cell Longev 2017.20174809751
[http://dx.doi.org/10.1155/2017/4809751 ] [PMID: 28286604]
[51]
Cadet JL, Ordonez SV, Ordonez JV. Methamphetamine induces apoptosis in immortalized neural cells: protection by the protooncogene, bcl-2. Synapse 1997; 25(2): 176-84.
[http://dx.doi.org/10.1002/(SICI)1098-2396(199702)25:2<176::AID-SYN8>3.0.CO;2-9 ] [PMID: 9021898]
[52]
Das J, Sil PC. Taurine ameliorates alloxan-induced diabetic renal injury, oxidative stress-related signaling pathways and apoptosis in rats. Amino Acids 2012; 43(4): 1509-23.
[http://dx.doi.org/10.1007/s00726-012-1225-y ] [PMID: 22302365]
[53]
Agca CA, Tuzcu M, Hayirli A, Sahin K. Taurine ameliorates neuropathy via regulating NF-κB and Nrf2/HO-1 signaling cascades in diabetic rats. Food Chem Toxicol 2014; 71: 116-21.
[http://dx.doi.org/10.1016/j.fct.2014.05.023 ] [PMID: 24907624]
[54]
Chen L, Chen YM, Wang LJ, et al. Higher homocysteine and lower betaine increase the risk of microangiopathy in patients with diabetes mellitus carrying the GG genotype of PEMT G774C. Diabetes Metab Res Rev 2013; 29(8): 607-17.
[http://dx.doi.org/10.1002/dmrr.2432 ] [PMID: 23794489]
[55]
Lever M, Slow S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem 2010; 43(9): 732-44.
[http://dx.doi.org/10.1016/j.clinbiochem.2010.03.009 ] [PMID: 20346934]
[56]
Yancey PH. Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 2005; 208(Pt 15): 2819-30.
[http://dx.doi.org/10.1242/jeb.01730 ] [PMID: 16043587]
[57]
Craig SA. Betaine in human nutrition. Am J Clin Nutr 2004; 80(3): 539-49.
[http://dx.doi.org/10.1093/ajcn/80.3.539 ] [PMID: 15321791]
[58]
Ross AB, Zangger A, Guiraud SP. Cereal foods are the major source of betaine in the Western diet-analysis of betaine and free choline in cereal foods and updated assessments of betaine intake. Food Chem 2014; 145: 859-65.
[http://dx.doi.org/10.1016/j.foodchem.2013.08.122 ] [PMID: 24128557]
[59]
Zabrodina VV, Shreder ED, Shreder OV, Durnev AD, Seredenin SB. Effect of Afobazole and Betaine on DNA Damage in Placental and Embryonic Tissues of Rats with Experimental Streptozocin Diabetes. Bull Exp Biol Med 2015; 159(6): 757-60.
[http://dx.doi.org/10.1007/s10517-015-3068-5 ] [PMID: 26519266]
[60]
da Costa KA, Niculescu MD, Craciunescu CN, Fischer LM, Zeisel SH. Choline deficiency increases lymphocyte apoptosis and DNA damage in humans. Am J Clin Nutr 2006; 84(1): 88-94.
[http://dx.doi.org/10.1093/ajcn/84.1.88 ] [PMID: 16825685]
[61]
Lever M, McEntyre CJ, George PM, et al. Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes. Cardiovasc Drugs Ther 2014; 28(5): 459-68.
[http://dx.doi.org/10.1007/s10557-014-6542-9 ] [PMID: 25060556]
[62]
Oulhaj A, Refsum H, Beaumont H, et al. Homocysteine as a predictor of cognitive decline in Alzheimer’s disease. Int J Geriatr Psychiatry 2010; 25(1): 82-90.
[PMID: 19484711]
[63]
Schartum-Hansen H, Ueland PM, Pedersen ER, et al. Assessment of urinary betaine as a marker of diabetes mellitus in cardiovascular patients. PLoS One 2013; 8(8): e69454.
[http://dx.doi.org/10.1371/journal.pone.0069454 ] [PMID: 23936331]
[64]
Suszynska J, Tisonczyk J, Lee HG, Smith MA, Jakubowski H. Reduced homocysteine-thiolactonase activity in Alzheimer’s disease. J Alzheimers Dis 2010; 19(4): 1177-83.
[http://dx.doi.org/10.3233/JAD-2010-1311 ] [PMID: 20308784]
[65]
Chai GS, Jiang X, Ni ZF, et al. Betaine attenuates Alzheimer-like pathological changes and memory deficits induced by homocysteine. J Neurochem 2013; 124(3): 388-96.
[http://dx.doi.org/10.1111/jnc.12094 ] [PMID: 23157378]
[66]
Eussen SJ, Ueland PM, Clarke R, et al. The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people. Br J Nutr 2007; 98(5): 960-8.
[http://dx.doi.org/10.1017/S0007114507750912 ] [PMID: 17537289]
[67]
Im AR, Kim YH, Uddin MR, et al. Betaine protects against rotenone-induced neurotoxicity in PC12 cells. Cell Mol Neurobiol 2013; 33(5): 625-35.
[http://dx.doi.org/10.1007/s10571-013-9921-z ] [PMID: 23605682]
[68]
Rabinowitch IM. Effects of Betaine Upon the Cholesterol and Bilirubin Contents of Blood Plasma in Diabetes Mellitus. Can Med Assoc J 1936; 34(6): 637-41.
[PMID: 20320277]
[69]
Schousboe A, Larsson OM, Sarup A, White HS. Role of the betaine/GABA transporter (BGT-1/GAT2) for the control of epilepsy. Eur J Pharmacol 2004; 500(1-3): 281-7.
[http://dx.doi.org/10.1016/j.ejphar.2004.07.032 ] [PMID: 15464040]
[70]
Slow S, Lever M, Chambers ST, George PM. Plasma dependent and independent accumulation of betaine in male and female rat tissues. Physiol Res 2009; 58(3): 403-10.
[PMID: 18637704]
[71]
Andrade S, Ramalho MJ, Loureiro JA, Pereira MDC. Natural Compounds for Alzheimer’s Disease Therapy: A Systematic Review of Preclinical and Clinical Studies. Int J Mol Sci 2019; 20(9): 2313.
[http://dx.doi.org/10.3390/ijms20092313 ] [PMID: 31083327]
[72]
Ohnishi T, Balan S, Toyoshima M, et al. Investigation of betaine as a novel psychotherapeutic for schizophrenia. EBioMedicine 2019; 45: 432-46.
[http://dx.doi.org/10.1016/j.ebiom.2019.05.062 ] [PMID: 31255657]
[73]
Kempson SA, Zhou Y, Danbolt NC. The betaine/GABA transporter and betaine: roles in brain, kidney, and liver. Front Physiol 2014; 5: 159.
[http://dx.doi.org/10.3389/fphys.2014.00159 ] [PMID: 24795654]
[74]
Petty CN, Lucero MT. Characterization of a Na+-dependent betaine transporter with Cl- channel properties in squid motor neurons. J Neurophysiol 1999; 81(4): 1567-74.
[http://dx.doi.org/10.1152/jn.1999.81.4.1567 ] [PMID: 10200192]
[75]
Bitoun M, Tappaz M. Gene expression of taurine transporter and taurine biosynthetic enzymes in brain of rats with acute or chronic hyperosmotic plasma. A comparative study with gene expression of myo-inositol transporter, betaine transporter and sorbitol biosynthetic enzyme. Brain Res Mol Brain Res 2000; 77(1): 10-8.
[http://dx.doi.org/10.1016/S0169-328X(00)00034-6 ] [PMID: 10814827]
[76]
Zhu XM, Ong WY. A light and electron microscopic study of betaine/GABA transporter distribution in the monkey cerebral neocortex and hippocampus. J Neurocytol 2004; 33(2): 233-40.
[http://dx.doi.org/10.1023/B:NEUR.0000030698.66675.90 ] [PMID: 15322381]
[77]
Takanaga H, Ohtsuki S. Hosoya Ki, Terasaki T. GAT2/BGT-1 as a system responsible for the transport of gamma-aminobutyric acid at the mouse blood-brain barrier. J Cereb Blood Flow Metab 2001; 21(10): 1232-9.
[http://dx.doi.org/10.1097/00004647-200110000-00012 ] [PMID: 11598501]
[78]
Zeisel SH. Choline: needed for normal development of memory. J Am Coll Nutr 2000; 19(5)(Suppl.): 528S-31.
[http://dx.doi.org/10.1080/07315724.2000.10718976 ] [PMID: 11023003]
[79]
Kunisawa K, Kido K, Nakashima N, Matsukura T, Nabeshima T, Hiramatsu M. Betaine attenuates memory impairment after waterimmersion restraint stress and is regulated by the GABAergic neuronal system in the hippocampus. Eur J Pharmacol 2017; 796: 122-30.
[http://dx.doi.org/10.1016/j.ejphar.2016.12.007 ] [PMID: 27940054]
[80]
Miwa M, Tsuboi M, Noguchi Y, Enokishima A, Nabeshima T, Hiramatsu M. Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2. J Neuroinflammation 2011; 8: 153.
[http://dx.doi.org/10.1186/1742-2094-8-153 ] [PMID: 22053950]
[81]
Zeisel SH, Niculescu MD. Perinatal choline influences brain structure and function. Nutr Rev 2006; 64(4): 197-203.
[http://dx.doi.org/10.1111/j.1753-4887.2006.tb00202.x ] [PMID: 16673755]
[82]
Zhang C-E, Tian Q, Wei W, et al. Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus. Neurobiol Aging 2008; 29(11): 1654-65.
[http://dx.doi.org/10.1016/j.neurobiolaging.2007.04.015 ] [PMID: 17537547]
[83]
Rowley NM, Smith MD, Lamb JG, Schousboe A, White HS. Hippocampal betaine/GABA transporter mRNA expression is not regulated by inflammation or dehydration post-status epilepticus. J Neurochem 2011; 117(1): 82-90.
[http://dx.doi.org/10.1111/j.1471-4159.2011.07174.x ] [PMID: 21219332]
[84]
Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998; 55(11): 1449-55.
[http://dx.doi.org/10.1001/archneur.55.11.1449 ] [PMID: 9823829]
[85]
McCaddon A, Davies G, Hudson P, Tandy S, Cattell H. Total serum homocysteine in senile dementia of Alzheimer type. Int J Geriatr Psychiatry 1998; 13(4): 235-9.
[http://dx.doi.org/10.1002/(SICI)1099-1166(199804)13:4<235::AID-GPS761>3.0.CO;2-8 ] [PMID: 9646150]
[86]
Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med 2002; 346(7): 476-83.
[http://dx.doi.org/10.1056/NEJMoa011613 ] [PMID: 11844848]
[87]
Ravaglia G, Forti P, Maioli F, et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr 2005; 82(3): 636-43.
[http://dx.doi.org/10.1093/ajcn/82.3.636 ] [PMID: 16155278]
[88]
Zhang C-E, Wei W, Liu Y-H, et al. Hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. Am J Pathol 2009; 174(4): 1481-91.
[http://dx.doi.org/10.2353/ajpath.2009.081036 ] [PMID: 19264913]
[89]
Pacheco-Quinto J, Rodriguez de Turco EB, DeRosa S, et al. Hyperhomocysteinemic Alzheimer’s mouse model of amyloidosis shows increased brain amyloid beta peptide levels. Neurobiol Dis 2006; 22(3): 651-6.
[http://dx.doi.org/10.1016/j.nbd.2006.01.005 ] [PMID: 16516482]
[90]
Kruman II, Culmsee C, Chan SL, et al. Homocysteine elicits a DNA damage response in neurons that promotes apoptosis and hypersensitivity to excitotoxicity. J Neurosci 2000; 20(18): 6920-6.
[http://dx.doi.org/10.1523/JNEUROSCI.20-18-06920.2000 ] [PMID: 10995836]
[91]
Reddy K, Cusack CL, Nnah IC, et al. Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency. Cell Rep 2016; 14(9): 2166-79.
[http://dx.doi.org/10.1016/j.celrep.2016.02.006 ] [PMID: 26923592]
[92]
Lowry CA, Smith DG, Siebler PH, et al. The Microbiota, Immunoregulation, and Mental Health: Implications for Public Health. Curr Environ Health Rep 2016; 3(3): 270-86.
[http://dx.doi.org/10.1007/s40572-016-0100-5 ] [PMID: 27436048]
[93]
Candela M, Biagi E, Brigidi P, O’Toole PW, De Vos WM. Maintenance of a healthy trajectory of the intestinal microbiome during aging: a dietary approach. Mech Ageing Dev 2014; 136-137: 70-5.
[http://dx.doi.org/10.1016/j.mad.2013.12.004 ] [PMID: 24373997]
[94]
Saraswati S, Sitaraman R. Aging and the human gut microbiota from correlation to causality. Front Microbiol 2015; 5: 764-4.
[http://dx.doi.org/10.3389/fmicb.2014.00764 ] [PMID: 25628610]
[95]
Tang WHW, Wang Z, Fan Y, et al. Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-Noxide in patients with heart failure: refining the gut hypothesis. J Am Coll Cardiol 2014; 64(18): 1908-14.
[http://dx.doi.org/10.1016/j.jacc.2014.02.617 ] [PMID: 25444145]
[96]
Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat Med 2013; 19(5): 576-85.
[http://dx.doi.org/10.1038/nm.3145 ] [PMID: 23563705]
[97]
Gao X, Liu X, Xu J, Xue C, Xue Y, Wang Y. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet. J Biosci Bioeng 2014; 118(4): 476-81.
[http://dx.doi.org/10.1016/j.jbiosc.2014.03.001 ] [PMID: 24721123]
[98]
Janeiro MH, Ramírez MJ, Milagro FI, Martínez JA, Solas M. Implication of Trimethylamine N-Oxide (TMAO) in Disease: Potential Biomarker or New Therapeutic Target. Nutrients 2018; 10(10): 1398.
[http://dx.doi.org/10.3390/nu10101398 ] [PMID: 30275434]
[99]
Li D, Ke Y, Zhan R, et al. Trimethylamine-N-oxide promotes brain aging and cognitive impairment in mice. Aging Cell 2018; 17(4): e12768-8.
[http://dx.doi.org/10.1111/acel.12768 ] [PMID: 29749694]
[100]
Li T, Chen Y, Gua C, Li X. Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress. Front Physiol 2017; 8: 350-0.
[http://dx.doi.org/10.3389/fphys.2017.00350 ] [PMID: 28611682]
[101]
Sui L, Wang J, Li B-M. Role of the phosphoinositide 3-kinase-Aktmammalian target of the rapamycin signaling pathway in long-term potentiation and trace fear conditioning memory in rat medial prefrontal cortex. Learn Mem 2008; 15(10): 762-76.
[http://dx.doi.org/10.1101/lm.1067808 ] [PMID: 18832563]
[102]
Tischmeyer W, Schicknick H, Kraus M, et al. Rapamycin-sensitive signalling in long-term consolidation of auditory cortex-dependent memory. Eur J Neurosci 2003; 18(4): 942-50.
[http://dx.doi.org/10.1046/j.1460-9568.2003.02820.x ] [PMID: 12925020]
[103]
Saha AK, Xu XJ, Balon TW, Brandon A, Kraegen EW, Ruderman NB. Insulin resistance due to nutrient excess: is it a consequence of AMPK downregulation? Cell Cycle 2011; 10(20): 3447-51.
[http://dx.doi.org/10.4161/cc.10.20.17886 ] [PMID: 22067655]
[104]
Querfurth HW, LaFerla FM. Alzheimer’s disease. N Engl J Med 2010; 362(4): 329-44.
[http://dx.doi.org/10.1056/NEJMra0909142 ] [PMID: 20107219]
[105]
Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong C-X. Brain glucose transporters, O-GlcNAcylation and phosphorylation of tau in diabetes and Alzheimer’s disease. J Neurochem 2009; 111(1): 242-9.
[http://dx.doi.org/10.1111/j.1471-4159.2009.06320.x ] [PMID: 19659459]
[106]
Jolivalt CG, Hurford R, Lee CA, Dumaop W, Rockenstein E, Masliah E. Type 1 diabetes exaggerates features of Alzheimer’s disease in APP transgenic mice. Exp Neurol 2010; 223(2): 422-31.
[http://dx.doi.org/10.1016/j.expneurol.2009.11.005 ] [PMID: 19931251]
[107]
Ke YD, Delerue F, Gladbach A, Götz J, Ittner LM. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer’s disease. PLoS One 2009; 4(11): e7917-7.
[http://dx.doi.org/10.1371/journal.pone.0007917 ] [PMID: 19936237]
[108]
Sims-Robinson C, Kim B, Rosko A, Feldman EL. How does diabetes accelerate Alzheimer disease pathology? Nat Rev Neurol 2010; 6(10): 551-9.
[http://dx.doi.org/10.1038/nrneurol.2010.130 ] [PMID: 20842183]
[109]
Steen E, Terry BM, Rivera EJ, et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease-is this type 3 diabetes? J Alzheimers Dis 2005; 7(1): 63-80.
[http://dx.doi.org/10.3233/JAD-2005-7107 ] [PMID: 15750215]
[110]
Caccamo A, Magrì A, Medina DX, et al. mTOR regulates tau phosphorylation and degradation: implications for Alzheimer’s disease and other tauopathies. Aging Cell 2013; 12(3): 370-80.
[http://dx.doi.org/10.1111/acel.12057 ] [PMID: 23425014]
[111]
Caccamo A, Majumder S, Richardson A, Strong R, Oddo S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 2010; 285(17): 13107-20.
[http://dx.doi.org/10.1074/jbc.M110.100420 ] [PMID: 20178983]
[112]
Majumder S, Richardson A, Strong R, Oddo S. Inducing autophagy by rapamycin before, but not after, the formation of plaques and tangles ameliorates cognitive deficits. PLoS One 2011; 6(9): e25416-6.
[http://dx.doi.org/10.1371/journal.pone.0025416 ] [PMID: 21980451]
[113]
Devi L, Alldred MJ, Ginsberg SD, Ohno M. Mechanisms underlying insulin deficiency-induced acceleration of β-amyloidosis in a mouse model of Alzheimer’s disease. PLoS One 2012; 7(3): e32792-2.
[http://dx.doi.org/10.1371/journal.pone.0032792 ] [PMID: 22403710]
[114]
Binder LI, Guillozet-Bongaarts AL, Garcia-Sierra F, Berry RW. Tau, tangles, and Alzheimer’s disease. Biochim Biophys Acta 2005; 1739(2-3): 216-23.
[http://dx.doi.org/10.1016/j.bbadis.2004.08.014 ] [PMID: 15615640]
[115]
Oddo S, Caccamo A, Shepherd JD, et al. Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron 2003; 39(3): 409-21.
[http://dx.doi.org/10.1016/S0896-6273(03)00434-3 ] [PMID: 12895417]
[116]
Singer MA, Lindquist S. Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell 1998; 1(5): 639-48.
[http://dx.doi.org/10.1016/S1097-2765(00)80064-7 ] [PMID: 9660948]
[117]
Crowe JH, Tablin F, Wolkers WF, Gousset K, Tsvetkova NM, Ricker J. Stabilization of membranes in human platelets freeze-dried with trehalose. Chem Phys Lipids 2003; 122(1-2): 41-52.
[http://dx.doi.org/10.1016/S0009-3084(02)00177-9 ] [PMID: 12598037]
[118]
Felice VD, Quigley EM, Sullivan AM, O’Keeffe GW, O’Mahony SM. Microbiota-gut-brain signalling in Parkinson’s disease: Implications for non-motor symptoms. Parkinsonism Relat Disord 2016; 27: 1-8.
[http://dx.doi.org/10.1016/j.parkreldis.2016.03.012 ] [PMID: 27013171]
[119]
Tanji K, Miki Y, Maruyama A, et al. Trehalose intake induces chaperone molecules along with autophagy in a mouse model of Lewy body disease. Biochem Biophys Res Commun 2015; 465(4): 746-52.
[http://dx.doi.org/10.1016/j.bbrc.2015.08.076 ] [PMID: 26299928]
[120]
Muller YL, Hanson RL, Knowler WC, et al. Identification of genetic variation that determines human trehalase activity and its association with type 2 diabetes. Hum Genet 2013; 132(6): 697-707.
[http://dx.doi.org/10.1007/s00439-013-1278-3 ] [PMID: 23468175]
[121]
Eze LC. Plasma trehalase activity and diabetes mellitus. Biochem Genet 1989; 27(9-10): 487-95.
[http://dx.doi.org/10.1007/BF02396146 ] [PMID: 2619709]
[122]
Martano G, Gerosa L, Prada I, et al. Biosynthesis of Astrocytic Trehalose Regulates Neuronal Arborization in Hippocampal Neurons. ACS Chem Neurosci 2017; 8(9): 1865-72.
[http://dx.doi.org/10.1021/acschemneuro.7b00177 ] [PMID: 28692243]
[123]
Clements RS Jr, Darnell B. Myo-inositol content of common foods: development of a high-myo-inositol diet. Am J Clin Nutr 1980; 33(9): 1954-67.
[http://dx.doi.org/10.1093/ajcn/33.9.1954 ] [PMID: 7416064]
[124]
Loewus MW, Loewus FA, Brillinger GU, Otsuka H, Floss HG. Stereochemistry of the myo-inositol-1-phosphate synthase reaction. J Biol Chem 1980; 255(24): 11710-2.
[PMID: 7002927]
[125]
Wong YH, Kalmbach SJ, Hartman BK, Sherman WR. Immunohistochemical staining and enzyme activity measurements show myo-inositol-1-phosphate synthase to be localized in the vasculature of brain. J Neurochem 1987; 48(5): 1434-42.
[http://dx.doi.org/10.1111/j.1471-4159.1987.tb05682.x ] [PMID: 2435847]
[126]
Di Daniel E, Cheng L, Maycox PR, Mudge AW. The common inositol-reversible effect of mood stabilizers on neurons does not involve GSK3 inhibition, myo-inositol-1-phosphate synthase or the sodium-dependent myo-inositol transporters. Mol Cell Neurosci 2006; 32(1-2): 27-36.
[http://dx.doi.org/10.1016/j.mcn.2006.01.015 ] [PMID: 16531065]
[127]
Shimon H, Sobolev Y, Davidson M, Haroutunian V, Belmaker RH, Agam G. Inositol levels are decreased in postmortem brain of schizophrenic patients. Biol Psychiatry 1998; 44(6): 428-32.
[http://dx.doi.org/10.1016/S0006-3223(98)00071-7 ] [PMID: 9777173]
[128]
Griffith HR, den Hollander JA, Okonkwo OC, O’Brien T, Watts RL, Marson DC. Brain metabolism differs in Alzheimer’s disease and Parkinson’s disease dementia. Alzheimers Dement 2008; 4(6): 421-7.
[http://dx.doi.org/10.1016/j.jalz.2008.04.008 ] [PMID: 19012867]
[129]
Fenili D, Brown M, Rappaport R, McLaurin J. Properties of scyllo-inositol as a therapeutic treatment of AD-like pathology. J Mol Med (Berl) 2007; 85(6): 603-11.
[http://dx.doi.org/10.1007/s00109-007-0156-7 ] [PMID: 17279347]
[130]
McLaurin J, Kierstead ME, Brown ME, et al. Cyclohexanehexol inhibitors of Abeta aggregation prevent and reverse Alzheimer phenotype in a mouse model. Nat Med 2006; 12(7): 801-8.
[http://dx.doi.org/10.1038/nm1423 ] [PMID: 16767098]
[131]
Frej AD, Otto GP, Williams RS. Tipping the scales: Lessons from simple model systems on inositol imbalance in neurological disorders. Eur J Cell Biol 2017; 96(2): 154-63.
[http://dx.doi.org/10.1016/j.ejcb.2017.01.007 ] [PMID: 28153412]
[132]
Kido K, Sato K, Makanae Y, Ato S, Hayashi T, Fujita S. Herbal supplement Kamishimotsuto augments resistance exercise-induced mTORC1 signaling in rat skeletal muscle. Nutrition 2016; 32(1): 108-13.
[http://dx.doi.org/10.1016/j.nut.2015.06.015 ] [PMID: 26423232]
[133]
Tseng HC, Graves DJ. Natural methylamine osmolytes, trimethylamine N-oxide and betaine, increase tau-induced polymerization of microtubules. Biochem Biophys Res Commun 1998; 250(3): 726-30.
[http://dx.doi.org/10.1006/bbrc.1998.9382 ] [PMID: 9784413]
[134]
Peluso G, Barbarisi A, Savica V, et al. Carnitine: an osmolyte that plays a metabolic role. J Cell Biochem 2000; 80(1): 1-10.
[http://dx.doi.org/10.1002/1097-4644(20010101)80:1<1::AID-JCB10>3.0.CO;2-W ] [PMID: 11029749]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy