α-Lipoic acid, functional fatty acid, as a novel therapeutic alternative for central nervous system diseases: A review

References

• Malińska D, Winiarska K. Lipoic acid: characteristics and therapeutic application. Postepy higieny i medycyny doswiadczalnej (online) 2004;59:535–43.
   Google Scholar
• Wollin SD, Jones PJ. α-Lipoic acid and cardiovascular disease. J Nutr 2003;133(11):3327–30.
   PubMed Web of Science ®Google Scholar
• Park S, Karunakaran U, Ho Jeoung N, Jeon J-H, Lee I-K. Physiological effect and therapeutic application of alpha lipoic acid. Curr Med Chem 2014;21(32):3636–45.
   PubMed Web of Science ®Google Scholar
• Singh U, Jialal I. Retracted: alpha-lipoic acid supplementation and diabetes. Nutr Rev 2008;66(11):646–57.
   PubMed Web of Science ®Google Scholar
• Lodge J, Youn H-D, Handelman G, Konishi T, Matsugo S, Mathur V, et al. Natural sources of lipoic acid: determination of lipoyllysine released from protease-digested tissues by high performance liquid chromatography incorporating electrochemical detection. J Appl Nutr 1997;49:3–11.
   Google Scholar
• Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition 2001;17(10):888–95.
   PubMed Web of Science ®Google Scholar
• Mayr JA, Zimmermann FA, Fauth C, Bergheim C, Meierhofer D, Radmayr D, et al. Lipoic acid synthetase deficiency causes neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation. Am J Hum Genet 2011;89(6):792–7.
   PubMed Web of Science ®Google Scholar
• Szeląg M, Mikulski D, Molski M. Quantum-chemical investigation of the structure and the antioxidant properties of α-lipoic acid and its metabolites. J Mol Model 2012;18(7):2907–16.
   PubMed Web of Science ®Google Scholar
• Biewenga GP, Haenen GR, Bast A. The pharmacology of the antioxidant lipoic acid. Gen Pharmacol Vasc S 1997;29(3):315–31.
   PubMedGoogle Scholar
• White SW, Zheng J, Zhang Y-M, Rock CO. The structural biology of type II fatty acid biosynthesis. Annu Rev Biochem 2005;74:791–831.
   PubMed Web of Science ®Google Scholar
• Holmquist L, Stuchbury G, Berbaum K, Muscat S, Young S, Hager K, et al. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol Ther 2007;113(1):154–64.
   PubMed Web of Science ®Google Scholar
• Haugaard N, Levin RM, Surname F. Regulation of the activity of choline acetyl transferase by lipoic acid. Mol Cell Biochem 2000;213(1–2):61–3.
   PubMed Web of Science ®Google Scholar
• Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 2009;1790(10):1149–60.
   PubMed Web of Science ®Google Scholar
• Ambrus A, Tretter L, Adam-Vizi V. Inhibition of the alpha-ketoglutarate dehydrogenase-mediated reactive oxygen species generation by lipoic acid. J Neurochem 2009;109(s1):222–9.
   PubMedGoogle Scholar
• Bustamante J, Lodge JK, Marcocci L, Tritschler HJ, Packer L, Rihn BH. α-Lipoic acid in liver metabolism and disease. Free Radic Biol Med 1998;24(6):1023–39.
   PubMed Web of Science ®Google Scholar
• Gilgun-Sherki Y, Melamed E, Offen D. Oxidative stress induced-neurodegenerative diseases: the need for antioxidants that penetrate the blood brain barrier. Neuropharmacology 2001;40(8):959–75.
   PubMed Web of Science ®Google Scholar
• Bilska A, Wlodek L. Lipoic acid-the drug of the future. Pharmacol Rep 2005;57(5):570–7.
   PubMed Web of Science ®Google Scholar
• Jones W, Li X, Qu Z-C, Perriott L, Whitesell RR, May JM. Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells. Free Radical Biol Med 2002;33(1):83–93.
   PubMed Web of Science ®Google Scholar
• Petersen Shay K, Moreau RF, Smith EJ, Hagen TM. Is α-lipoic acid a scavenger of reactive oxygen species in vivo? Evidence for its initiation of stress signaling pathways that promote endogenous antioxidant capacity. IUBMB Life 2008;60(6):362–7.
   PubMed Web of Science ®Google Scholar
• Collins T, Read M, Neish A, Whitley M, Thanos D, Maniatis T. Transcriptional regulation of endothelial cell adhesion molecules: NF-kappa B and cytokine-inducible enhancers. FASEB J 1995;9(10):899–909.
   PubMed Web of Science ®Google Scholar
• Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 2000;18(1):621–63.
   PubMed Web of Science ®Google Scholar
• Zhang W-J, Frei B. α-Lipoic acid inhibits TNF-α-induced NF-κB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 2001;15(13):2423–32.
   PubMed Web of Science ®Google Scholar
• Chaudhary P, Marracci GH, Bourdette DN. Lipoic acid inhibits expression of ICAM-1 and VCAM-1 by CNS endothelial cells and T cell migration into the spinal cord in experimental autoimmune encephalomyelitis. J Neuroimmunol 2006;175(1):87–96.
   PubMed Web of Science ®Google Scholar
• Kim H, Kim H, Park K, Kim Y, Kwon T, Park J, et al. Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity. Exp Mol Med 2007;39(1):106–13.
   PubMed Web of Science ®Google Scholar
• Abdelkarem HM, Fadda LH, Hassan AA. Potential intervention of α-lipoic acid and carnitine on insulin sensitivity and anti-inflammatory cytokines levels in fructose-fed rats, a model of metabolic syndrome. J Diet Suppl 2017;14(1):54–64.
   PubMedGoogle Scholar
• Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, et al. Lipoic acid reduces expression of vascular cell adhesion molecule-I and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci 1999;96:75–82.
   PubMed Web of Science ®Google Scholar
• Guo J, Gao S, Liu Z, Zhao R, Yang X. Alpha-lipoic acid alleviates acute inflammation and promotes lipid mobilization during the inflammatory response in white adipose tissue of mice. Lipids 2016;51(10):1145–52.
   PubMed Web of Science ®Google Scholar
• Valko M, Morris H, Cronin M. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12(10):1161–208.
   PubMed Web of Science ®Google Scholar
• Ou P, Tritschler HJ, Wolff SP. Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant? Biochem Pharmacol 1995;50(1):123–6.
   PubMed Web of Science ®Google Scholar
• Lodge JK, Traber MG, Packer L. Thiol chelation of Cu2 by dihydrolipoic acid prevents human low density lipoprotein peroxidation. Free Radical Biol Med 1998;25(3):287–97.
   PubMed Web of Science ®Google Scholar
• Bush AI. Metal complexing agents as therapies for Alzheimer’s disease. Neurobiol Aging 2002;23(6):1031–8.
   PubMed Web of Science ®Google Scholar
• Goralska M, Dackor R, Holley B, McGahan MC. Alpha lipoic acid changes iron uptake and storage in lens epithelial cells. Exp Eye Res 2003;76(2):241–8.
   PubMed Web of Science ®Google Scholar
• Suh JH, Moreau R, Heath S-HD, Hagen TM. Dietary supplementation with (R)-α-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep 2005;10(1):52–60.
   PubMed Web of Science ®Google Scholar
• Hermann R, Niebch G, Borbe H, Fieger-Büschges H, Ruus P, Nowak H, et al. Enantioselective pharmacokinetics and bioavailability of different racemic α-lipoic acid formulations in healthy volunteers. Eur J Pharm Sci 1996;4(3):167–74.
   Web of Science ®Google Scholar
• Teichert J, Hermann R, Ruus P, Preiss R. Plasma kinetics, metabolism, and urinary excretion of alpha-lipoic acid following oral administration in healthy volunteers. J Clin Pharmacol 2003;43(11):1257–67.
   PubMed Web of Science ®Google Scholar
• Teichert J, Kern J, Tritschler H, Ulrich H, Preiss R. Investigations on the pharmacokinetics of alpha-lipoic acid in healthy volunteers. Int J Clin Pharmacol Ther 1998;36(12):625–8.
   PubMed Web of Science ®Google Scholar
• Carlson DA, Smith AR, Fischer SJ, Young KL, Packer L. The plasma pharmacokinetics of R-(+)-lipoic acid administered as sodium R-(+)-lipoate to healthy human subjects. Altern Med Rev 2007;12(4):343.
   PubMedGoogle Scholar
• Gleiter C, Schug B, Hermann R, Elze M, Blume H, Gundert-Remy U. Influence of food intake on the bioavailability of thioctic acid enantiomers. Eur J Clin Pharmacol 1996;50(6):513–4.
   PubMed Web of Science ®Google Scholar
• Packer L, Witt EH, Tritschler HJ. Alpha-lipoic acid as a biological antioxidant. Free Radical Biol Med 1995;19(2):227–50.
   PubMed Web of Science ®Google Scholar
• Hill A, Werner J, Rogers Q, O’Neill S, Christopher M. Lipoic acid is 10 times more toxic in cats than reported in humans, dogs or rats. J Anim Physiol Anim Nutr 2004;88(3–4):150–6.
   PubMed Web of Science ®Google Scholar
• Cremer D, Rabeler R, Roberts A, Lynch B. Long-term safety of α-lipoic acid (ALA) consumption: a 2-year study. Regul Toxicol Pharmacol 2006;46(3):193–201.
   PubMed Web of Science ®Google Scholar
• Çakatay U, Kayaliı R. Plasma protein oxidation in aging rats after alpha-lipoic acid administration. Biogerontology 2005;6(2):87–93.
   PubMed Web of Science ®Google Scholar
• Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Möller W, et al. Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (α-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Free Radic Res 1999;31(3):171–9.
   PubMed Web of Science ®Google Scholar
• Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy the NATHAN 1 trial. Diabetes Care 2011;34(9):2054–60.
   PubMed Web of Science ®Google Scholar
• Comabella M, Khoury SJ. Immunopathogenesis of multiple sclerosis. Clin Immunol 2012;142(1):2–8.
   PubMed Web of Science ®Google Scholar
• Chaudhary P, Marracci G, Yu X, Galipeau D, Morris B, Bourdette D. Lipoic acid decreases inflammation and confers neuroprotection in experimental autoimmune optic neuritis. J Neuroimmunol 2011;233(1):90–6.
   PubMed Web of Science ®Google Scholar
• Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, et al. Lipoic acid in multiple sclerosis: a pilot study. Mult Scler J 2005;11(2):159–65.
   PubMed Web of Science ®Google Scholar
• Owens S. Lipoic acid therapy found to slow rate of brain atrophy. Neurology Today 2016; Sep 18.
   PubMedGoogle Scholar
• Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, et al. Lipoic acid affects cellular migration into the central nervous system and stabilizes blood-brain barrier integrity. J Immunol 2006;177(4):2630–7.
   PubMed Web of Science ®Google Scholar
• Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003;9(6):540–9.
   PubMed Web of Science ®Google Scholar
• Morini M, Roccatagliata L, Dell’Eva R, Pedemonte E, Furlan R, Minghelli S, et al. α-Lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol 2004;148(1):146–53.
   PubMed Web of Science ®Google Scholar
• Marracci GH, Jones RE, McKeon GP, Bourdette DN. Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol 2002;131(1):104–14.
   PubMed Web of Science ®Google Scholar
• Chaudhary P, Marracci G, Galipeau D, Pocius E, Morris B, Bourdette D. Lipoic acid reduces inflammation in a mouse focal cortical experimental autoimmune encephalomyelitis model. J Neuroimmunol 2015;289:68–74.
   PubMed Web of Science ®Google Scholar
• Taupin P. Adult neurogenesis, neuroinflammation and therapeutic potential of adult neural stem cells. Int J Med Sci 2008;5(3):127–32.
   PubMedGoogle Scholar
• Smith K. Pathophysiology of multiple sclerosis. La Revue du Praticien 2006;56(12):1299–303.
   PubMedGoogle Scholar
• Salinthone S, Yadav V, Schillace RV, Bourdette DN, Carr DW. Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PLoS One 2010;5(9):e13058.
   PubMed Web of Science ®Google Scholar
• van der Goes A, Brouwer J, Hoekstra K, Roos D, van den Berg TK, Dijkstra CD. Reactive oxygen species are required for the phagocytosis of myelin by macrophages. J Neuroimmunol 1998;92(1):67–75.
   PubMed Web of Science ®Google Scholar
• Khalili M, Eghtesadi S, Mirshafiey A, Eskandari G, Sanoobar M, Sahraian MA, et al. Effect of lipoic acid consumption on oxidative stress among multiple sclerosis patients: a randomized controlled clinical trial. Nutr Neurosci 2014;17(1):16–20.
   PubMed Web of Science ®Google Scholar
• Khalili M, Azimi A, Izadi V, Eghtesadi S, Mirshafiey A, Sahraian M, et al. Does lipoic acid consumption affect the cytokine profile in multiple sclerosis patients: a double-blind, placebo-controlled, randomized clinical trial. Neuroimmunomodulation 2014;21(6):291–6.
   PubMed Web of Science ®Google Scholar
• Yadav V, Marracci GH, Munar MY, Cherala G, Stuber LE, Alvarez L, et al. Pharmacokinetic study of lipoic acid in multiple sclerosis: comparing mice and human pharmacokinetic parameters. Mult Scler 2010;16(4):387–97.
   PubMed Web of Science ®Google Scholar
• Khalili M, Eskandari G, Ghajarzadeh M, Azimi A, Eghtesadi S, Sahraian MA, et al. Lipoic acid and multiple sclerosis: a randomized controlled clinical trial. Curr Top Nutraceutical Res 2012;10(2):95–9.
   Web of Science ®Google Scholar
• Gazewood JD, Richards DR, Clebak K. Parkinson disease: an update. Am Fam Physician 2013;87(4):267–73.
   PubMed Web of Science ®Google Scholar
• Henchcliffe C, Beal MF. Mitochondrial biology and oxidative stress in Parkinson disease pathogenesis. Nat Clin Pract Neuro 2008;4(11):600–9.
   PubMedGoogle Scholar
• Kidd PM. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. Altern Med Rev 2005;10(4):268.
   PubMedGoogle Scholar
• Chaudhuri KR, Schapira AH. Non-motor symptoms of Parkinson’s disease: dopaminergic pathophysiology and treatment. Lancet Neurol 2009;8(5):464–74.
   PubMed Web of Science ®Google Scholar
• Araújo DP D, Lobato RDFG, Cavalcanti JRLDP, Sampaio LRL, Araújo PVP, Silva MCC, et al. The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson’s disease: a review. Int J Neurosci 2011;121(2):51–7.
   PubMed Web of Science ®Google Scholar
• Jalali-Nadoushan M, Roghani M. Alpha-lipoic acid protects against 6-hydroxydopamine-induced neurotoxicity in a rat model of hemi-parkinsonism. Brain Res 2013;1505:68–74.
   PubMed Web of Science ®Google Scholar
• Santos ÍMDS, Freitas RLMD, Saldanha GB, Tomé ADR, Jordán J, Freitas RMD. Alterations on monoamines concentration in rat hippocampus produced by lipoic acid. Arquivos de Neuro-Psiquiatria 2010;68(3):362–6.
   PubMed Web of Science ®Google Scholar
• Karunakaran S, Diwakar L, Saeed U, Agarwal V, Ramakrishnan S, Iyengar S, et al. Activation of apoptosis signal regulating kinase 1 (ASK1) and translocation of death-associated protein, Daxx, in substantia nigra pars compacta in a mouse model of Parkinson’s disease: protection by α-lipoic acid. FASEB J 2007;21(9):2226–36.
   PubMed Web of Science ®Google Scholar
• Li D-W, Li G-R, Lu Y, Liu Z-Q, Chang M, Yao M, et al. α-Lipoic acid protects dopaminergic neurons against MPP+-induced apoptosis by attenuating reactive oxygen species formation. Int J Mol Med 2013;32(1):108–14.
   PubMed Web of Science ®Google Scholar
• Aguiar LMV, Nobre HV, Macêdo DS, Oliveira AA, Freitas RM, Vasconcelos SM, et al. Neuroprotective effects of caffeine in the model of 6-hydroxydopamine lesion in rats. Pharmacol Biochem Behav 2006;84(3):415–9.
   PubMed Web of Science ®Google Scholar
• Kulich SM, Chu CT. Role of reactive oxygen species in extracellular signal-regulated protein kinase phosphorylation and 6-hydroxydopamine cytotoxicity. J Biosci 2003;28(1):83–9.
   PubMed Web of Science ®Google Scholar
• Moore DJ, West AB, Dawson VL, Dawson TM. Molecular pathophysiology of Parkinson’s disease. Annu Rev Neurosci 2005;28:57–87.
   PubMed Web of Science ®Google Scholar
• Packer L, Cadenas E. Lipoic acid: energy metabolism and redox regulation of transcription and cell signaling. J Clin Biochem Nutr 2011;48(1):26.
   PubMed Web of Science ®Google Scholar
• Zhang H, Jia H, Liu J, Ao N, Yan B, Shen W, et al. Combined R-α–lipoic acid and acetyl-L-carnitine exerts efficient preventative effects in a cellular model of Parkinson’s disease. J Cell Mol Med 2010;14(1-2):215–25.
   PubMed Web of Science ®Google Scholar
• Ferreira P, Militão G, Freitas R. Lipoic acid effects on lipid peroxidation level, superoxide dismutase activity and monoamines concentration in rat hippocampus. Neurosci Lett 2009;464(2):131–4.
   PubMed Web of Science ®Google Scholar
• Tamaoka A. The pathophysiology of Alzheimer’s disease with special reference to “amyloid cascade hypothesis”. Rinsho Byori 2013;61(11):1060–9.
   PubMedGoogle Scholar
• Nordberg A. In vivo detection of neurotransmitter changes in Alzheimer’s disease. Ann NY Acad Sci 1993;695(1):27–33.
   PubMedGoogle Scholar
• Whitehouse PJ, Au KS. Cholinergic receptors in aging and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 1986;10(3):665–76.
   PubMed Web of Science ®Google Scholar
• Tomaszewicz M, Roßner S, Schliebs R, Ćwikowska J, Szutowicz A. Changes in cortical acetyl-CoA metabolism after selective basal forebrain cholinergic degeneration by 192IgG-saporin. J Neurochem 2003;87(2):318–24.
   PubMed Web of Science ®Google Scholar
• Fu W, Jhamandas JH. Role of astrocytic glycolytic metabolism in Alzheimer’s disease pathogenesis. Biogerontology 2014;15(6):579–86.
   PubMed Web of Science ®Google Scholar
• Avila-Muñoz E, Arias C. When astrocytes become harmful: functional and inflammatory responses that contribute to Alzheimer’s disease. Ageing Res Rev. 2014;18:29–40.
   PubMed Web of Science ®Google Scholar
• Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH. Mitochondria are a direct site of Aβ accumulation in Alzheimer’s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Gen 2006;15(9):1437–49.
   PubMed Web of Science ®Google Scholar
• Butterfield DA, Boyd-Kimball D, Castegna A. Proteomics in Alzheimer’s disease: insights into potential mechanisms of neurodegeneration. J Neurochem 2003;86(6):1313–27.
   PubMed Web of Science ®Google Scholar
• Lovell MA, Markesbery WR. Oxidative damage in mild cognitive impairment and early Alzheimer’s disease. J Neurosci Res 2007;85(14):3036–40.
   PubMed Web of Science ®Google Scholar
• Stuchbury G, Münch G. Alzheimer’s associated inflammation, potential drug targets and future therapies. J Neural Transm 2005;112(3):429–53.
   PubMed Web of Science ®Google Scholar
• Morris M. The role of nutrition in Alzheimer’s disease: epidemiological evidence. Eur J Neurol 2009;16(s1):1–7.
   PubMedGoogle Scholar
• Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, et al. Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 2012;69(7):836–41.
   PubMedGoogle Scholar
• Griffin WST, Sheng JG, Roberts GW, Mrak RE. Interleukin-1 expression in different plaque types in Alzheimer’s disease: significance in plaque evaluation. J Neuropathol Exp Neurol 1995;54(2):276–81.
   PubMed Web of Science ®Google Scholar
• Farr SA, Price TO, Banks WA, Ercal N, Morley JE. Effect of alpha-lipoic acid on memory, oxidation, and lifespan in SAMP8 mice. J Alzheimers Dis 2012;32(2):447–55.
   PubMed Web of Science ®Google Scholar
• Moraes TB, Dalazen GR, Jacques CE, de Freitas RS, Rosa AP, Dutra-Filho CS. Glutathione metabolism enzymes in brain and liver of hyperphenylalaninemic rats and the effect of lipoic acid treatment. Metab Brain Dis 2014;29(3):609–15.
   PubMed Web of Science ®Google Scholar
• Pocernich CB, Butterfield DA. Acrolein inhibits NADH-linked mitochondrial enzyme activity: implications for Alzheimer’s disease. Neurotox Res 2003;5(7):515–9.
   PubMed Web of Science ®Google Scholar
• Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-α-lipoic acid on mitochondrial enzymes in aged rats. Chem Biol Interact 2001;138(2):189–98.
   PubMed Web of Science ®Google Scholar
• Ajith TA, Nima N, Veena RK, Janardhanan KK, Antonawich F. Effect of palladium α-lipoic acid complex on energy in the brain mitochondria of aged rats. Altern Ther Health Med 2013;20(3):27–35.
   Web of Science ®Google Scholar
• Huang X, Atwood CS, Hartshorn MA, Multhaup G, Goldstein LE, Scarpa RC, et al. The Aβ peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 1999;38(24):7609–16.
   PubMed Web of Science ®Google Scholar
• Suh JH, Zhu B-Z, deSzoeke E, Frei B, Hagen TM. Dihydrolipoic acid lowers the redox activity of transition metal ions but does not remove them from the active site of enzymes. Redox Rep 2004;9(1):57–61.
   PubMed Web of Science ®Google Scholar
• Fonte J, Miklossy J, Atwood C, Martins R. The severity of cortical Alzheimer’s type changes is positively correlated with increased amyloid-β levels: resolubilization of amyloid-β with transition metal ion chelators. J Alzheimers Dis 2001;3(2):209–19.
   PubMed Web of Science ®Google Scholar
• Sancheti H, Akopian G, Yin F, Brinton RD, Walsh JP, Cadenas E. Age-dependent modulation of synaptic plasticity and insulin mimetic effect of lipoic acid on a mouse model of Alzheimer’s disease. PloS one 2013;8(7):e69830.
   PubMed Web of Science ®Google Scholar
• Haugaard N, Levin RM. Activation of choline acetyl transferase by dihydrolipoic acid. Mol Cell Biochem 2002;229(1–2):103–6.
   PubMed Web of Science ®Google Scholar
• de Freitas RM. Lipoic acid increases hippocampal choline acetyltransferase and acetylcholinesterase activities and improvement memory in epileptic rats. Neurochem Res 2010;35(1):162–70.
   PubMed Web of Science ®Google Scholar
• Jiang T, Yin F, Yao J, Brinton RD, Cadenas E. Lipoic acid restores age-associated impairment of brain energy metabolism through the modulation of Akt/JNK signaling and PGC1α transcriptional pathway. Aging Cell 2013;12(6):1021–31.
   PubMed Web of Science ®Google Scholar
• Stough CKK, Scholey A. Advances in natural medicines, nutraceuticals and neurocognition. London: CRC Press; 2013.
   Google Scholar
• Maczurek A, Hager K, Kenklies M, Sharman M, Martins R, Engel J, et al. Lipoic acid as an anti-inflammatory and neuroprotective treatment for Alzheimer’s disease. Adv Drug Deliv Rev 2008;60(13):1463–70.
   PubMed Web of Science ®Google Scholar
• Hoyer S. Memory function and brain glucose metabolism. Pharmacopsychiatry 2003;36:62–7.
   Web of Science ®Google Scholar
• Sweeney MI, Waiz W, Yager JY, Juurlink B. Cellular mechanisms involved in brain ischemia. Can J Physiol Pharmacol 1995;73(11):1525–35.
   PubMed Web of Science ®Google Scholar
• Gilgun-Sherki Y, Rosenbaum Z, Melamed E, Offen D. Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 2002;54(2):271–84.
   PubMed Web of Science ®Google Scholar
• Chamorro Á, Dirnagl U, Urra X, Planas AM. Neuroprotection in acute stroke: targeting excitotoxicity, oxidative and nitrosative stress, and inflammation. Lancet Neurol 2016;15(8):869–81.
   PubMed Web of Science ®Google Scholar
• Shaafi S, Afrooz MR, Hajipour B, Dadadshi A, Hosseinian MM, Khodadadi A. Anti-oxidative effect of lipoic acid in spinal cord ischemia/reperfusion. Med Princ Pract 2010;20(1):19–22.
   PubMed Web of Science ®Google Scholar
• Panigrahi M, Sadguna Y, Shivakumar BR, Kolluri SV, Roy S, Packer L, et al. α-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Brain Res 1996;717(1):184–8.
   PubMed Web of Science ®Google Scholar
• Wolz P, Krieglstein J. Neuroprotective effects of α-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Neuropharmacology 1996;35(3):369–75.
   PubMed Web of Science ®Google Scholar
• Connell BJ, Saleh M, Khan BV, Saleh TM. Lipoic acid protects against reperfusion injury in the early stages of cerebral ischemia. Brain Res 2011;1375:128–36.
   PubMed Web of Science ®Google Scholar
• Choi K-H, Park M-S, Kim H-S, Kim K-T, Kim H-S, Kim J-T, et al. Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats. Mol Brain 2015;8(1):9–25.
   PubMedGoogle Scholar
• Clark WM, Rinker LG, Lessov NS, Lowery SL, Cipolla MJ. Efficacy of antioxidant therapies in transient focal ischemia in mice. Stroke 2001;32(4):1000–4.
   PubMed Web of Science ®Google Scholar
• Cao X, Phillis JW. The free radical scavenger, α-lipoic acid, protects against cerebral ischemia-reperfusion injury in gerbils. Free Radic Res 1995;23(4):365–70.
   PubMed Web of Science ®Google Scholar
• Lipton P. Ischemic cell death in brain neurons. Physiol Rev 1999;79(4):1431–568.
   PubMed Web of Science ®Google Scholar
• Richard MJ, Connell BJ, Khan BV, Saleh TM. Cellular mechanisms by which lipoic acid confers protection during the early stages of cerebral ischemia: a possible role for calcium. Neurosci Res 2011;69(4):299–307.
   PubMed Web of Science ®Google Scholar
• Azbill RD, Mu X, Bruce-Keller AJ, Mattson MP, Springer JE. Impaired mitochondrial function, oxidative stress and altered antioxidant enzyme activities following traumatic spinal cord injury. Brain Res 1997;765(2):283–90.
   PubMed Web of Science ®Google Scholar
• Toklu HZ, Hakan T, Celik H, Biber N, Erzik C, Ogunc AV, et al. Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats. J Spinal Cord Med 2010;33(4):401–9.
   PubMed Web of Science ®Google Scholar
• Slemmer JE, Shacka JJ, Sweeney M, Weber JT. Antioxidants and free radical scavengers for the treatment of stroke, traumatic brain injury and aging. Curr Med Chem 2008;15(4):404–14.
   PubMed Web of Science ®Google Scholar
• Emmez H, Yildirim Z, Kale A, Tönge M, Durdağ E, Börcek AÖ, et al. Anti-apoptotic and neuroprotective effects of alpha-lipoic acid on spinal cord ischemia–reperfusion injury in rabbits. Acta Neurochir 2010;152(9):1591–601.
   PubMed Web of Science ®Google Scholar
• Bernards C, Akers T. Effect of postinjury intravenous or intrathecal methylprednisolone on spinal cord excitatory amino-acid release, nitric oxide generation, PGE2 synthesis, and myeloperoxidase content in a pig model of acute spinal cord injury. Spinal Cord 2006;44(10):594–604.
   PubMed Web of Science ®Google Scholar
• Taoka Y, Okajima K, Uchiba M, Johno M. Methylprednisolone reduces spinal cord injury in rats without affecting tumor necrosis factor-α production. J Neurotrauma 2001;18(5):533–43.
   PubMed Web of Science ®Google Scholar
• Tas N, Bakar B, Kasimcan MO, Gazyagci S, Ayva SK, Kılınc K, et al. Evaluation of protective effects of the alpha lipoic acid after spinal cord injury: An animal study. Injury 2010;41(10):1068–74.
   PubMed Web of Science ®Google Scholar
• Mohammadi V, Khalili M, Eghtesadi S, Dehghani S, Jazayeri S, Aghababaee S, et al. The effect of alpha-lipoic acid (ALA) supplementation on cardiovascular risk factors in men with chronic spinal cord injury: a clinical trial. Spinal Cord. 2015;53:621–4.
   PubMed Web of Science ®Google Scholar