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Lipoic Acid, Inflammation and Diseases of the Nervous System

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Systems Biology of Free Radicals and Antioxidants

Abstract

Oxidative stress and inflammation are normal biological processes that are implicated in the pathogenesis of many neurological diseases such as multiple sclerosis, cerebral ischemia, stroke, epilepsy, and diabetic neuropathy. Treatment with compounds that can block these processes has the potential to be therapeutically effective. Lipoic acid is a naturally occurring supplement that appears to act both as an antioxidant and an anti-inflammatory agent. This chapter reviews the current data on the effectiveness of LA for each of the above-mentioned diseases and also examines the possible mechanisms of actions that allow LA to function as a therapeutic agent.

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References

  • Abdul HM, Butterfield DA (2007) Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: implications for Alzheimer’s disease. Free Radic Biol Med 42:371–384

    PubMed  PubMed Central  Google Scholar 

  • Ametov AS, Barinov A, Dyck PJ, Hermann R, Kozlova N, Litchy WJ, Low PA, Nehrdich D, Novosadova M, O’Brien PC, Reljanovic M, Samigullin R, Schuette K, Strokov I, Tritschler HJ, Wessel K, Yakhno N, Ziegler D (2003) The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial. Diabetes Care 26:770–776

    CAS  PubMed  Google Scholar 

  • Bermel RA, Rudick RA (2007) Interferon-beta treatment for multiple sclerosis. Neurotherapeutics 4:633–646

    CAS  PubMed  Google Scholar 

  • Chaudhary P, Marracci GH, Bourdette DN (2006) 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 175:87–96

    CAS  PubMed  Google Scholar 

  • Chofflon M (2005) Mechanisms of action for treatments in multiple sclerosis: does a heterogeneous disease demand a multi-targeted therapeutic approach? BioDrugs 19:299–308

    CAS  PubMed  Google Scholar 

  • Connell BJ, Saleh M, Khan BV, Saleh TM (2010) Lipoic acid protects against reperfusion injury in the early stages of cerebral ischemia. Brain Res 1375:128–136

    PubMed  Google Scholar 

  • de Freitas RM (2010a) Lipoic acid alters delta-aminolevulinic dehydratase, glutathione peroxidase and Na+, K+−ATPase activities and glutathione-reduced levels in rat hippocampus after pilocarpine-induced seizures. Cell Mol Neurobiol 30:381–387

    CAS  PubMed  Google Scholar 

  • de Freitas RM (2010b) Lipoic acid increases hippocampal choline acetyltransferase and acetylcholinesterase activities and improvement memory in epileptic rats. Neurochem Res 35:162–170

    PubMed  Google Scholar 

  • de Freitas RM, Gomes KN, Saldanha GB (2011) Neuropharmacological effects of lipoic acid and ubiquinone on the mRNA level of interleukin-1beta and acetylcholinesterase activity in rat hippocampus after seizures. Fundam Clin Pharmacol 25:354–361

    PubMed  Google Scholar 

  • Dittel BN (2008) CD4 T cells: balancing the coming and going of autoimmune-mediated inflammation in the CNS. Brain Behav Immun 22:421–430

    CAS  PubMed  PubMed Central  Google Scholar 

  • dos Santos PS, Feitosa CM, Saldanha GB, Tome Ada R, Feng D, de Freitas RM (2011) Lipoic acid inhibits caspase-dependent and -independent cell death pathways and is neuroprotective against hippocampal damage after pilocarpine-induced seizures. Pharmacol Biochem Behav 97:531–536

    PubMed  Google Scholar 

  • Duby JJ, Campbell RK, Setter SM, White JR, Rasmussen KA (2004) Diabetic neuropathy: an intensive review. Am J Health Syst Pharm 61:160–173; quiz 175–176

    CAS  PubMed  Google Scholar 

  • Duchen LW, Anjorin A, Watkins PJ, Mackay JD (1980) Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med 92:301–303

    CAS  PubMed  Google Scholar 

  • Engelhardt B, Ransohoff RM (2005) The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol 26:485–495

    CAS  PubMed  Google Scholar 

  • Estrada DE, Ewart HS, Tsakiridis T, Volchuk A, Ramlal T, Tritschler H, Klip A (1996) Stimulation of glucose uptake by the natural coenzyme alpha-lipoic acid/thioctic acid: participation of elements of the insulin signaling pathway. Diabetes 45:1798–1804

    CAS  PubMed  Google Scholar 

  • Fonte J, Miklossy J, Atwood C, Martins R (2001) The severity of cortical Alzheimer’s type changes is positively correlated with increased amyloid-beta levels: resolubilization of amyloid-beta with transition metal ion chelators. J Alzheimers Dis 3:209–219

    CAS  PubMed  Google Scholar 

  • Friedman A, Dingledine R (2011) Molecular cascades that mediate the influence of inflammation on epilepsy. Epilepsia 52(3):33–39

    CAS  PubMed  PubMed Central  Google Scholar 

  • Furlan AJ, Katzan IL, Caplan LR (2003) Thrombolytic therapy in acute ischemic stroke. Curr Treat Options Cardiovasc Med 5:171–180

    PubMed  Google Scholar 

  • Galasko D, Montine TJ (2010) Biomarkers of oxidative damage and inflammation in Alzheimer’s disease. Biomark Med 4:27–36

    CAS  PubMed  PubMed Central  Google Scholar 

  • Galasko DR, Peskind E, Clark CM, Quinn JF, Ringman JM, Jicha GA, Cotman C, Cottrell B, Montine TJ, Thomas RG, Aisen P (2012) Antioxidants for Alzheimer disease: a randomized clinical trial with cerebrospinal fluid biomarker measures. Arch Neurol 69:836–841

    PubMed  PubMed Central  Google Scholar 

  • Gilgun-Sherki Y, Melamed E, Offen D (2004) The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 251:261–268

    CAS  PubMed  Google Scholar 

  • Glabinski A, Tawsek NS, Bartosz G (1993) Increased generation of superoxide radicals in the blood of MS patients. Acta Neurol Scand 88:174–177

    CAS  PubMed  Google Scholar 

  • Gonzalez-Clemente JM, Mauricio D, Richart C, Broch M, Caixas A, Megia A, Gimenez-Palop O, Simon I, Martinez-Riquelme A, Gimenez-Perez G, Vendrell J (2005) Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus. Clin Endocrinol 63:525–529

    CAS  Google Scholar 

  • Guy J, Ellis EA, Hope GM, Rao NA (1989) Antioxidant enzyme suppression of demyelination in experimental optic neuritis. Curr Eye Res 8:467–477

    CAS  PubMed  Google Scholar 

  • Guy J, Ellis EA, Mames R, Rao NA (1993) Role of hydrogen peroxide in experimental optic neuritis. A serial quantitative ultrastructural study. Ophthalmic Res 25:253–264

    CAS  PubMed  Google Scholar 

  • Hagen TM, Ingersoll RT, Lykkesfeldt J, Liu J, Wehr CM, Vinarsky V, Bartholomew JC, Ames AB (1999) (R)-alpha-lipoic acid-supplemented old rats have improved mitochondrial function, decreased oxidative damage, and increased metabolic rate. FASEB J 13:411–418

    CAS  PubMed  Google Scholar 

  • Hager K, Marahrens A, Kenklies M, Riederer P, Munch G (2001) Alpha-lipoic acid as a new treatment option for Alzheimer type dementia. Arch Gerontol Geriatr 32:275–282

    CAS  PubMed  Google Scholar 

  • Hager K, Kenklies M, McAfoose J, Engel J, Munch G (2007) Alpha-lipoic acid as a new treatment option for Alzheimer’s disease–a 48 months follow-up analysis. J Neural Transm Suppl 72:189–193

    CAS  PubMed  Google Scholar 

  • Hartung HP, Schafer B, Heininger K, Toyka KV (1988) Suppression of experimental autoimmune neuritis by the oxygen radical scavengers superoxide dismutase and catalase. Ann Neurol 23:453–460

    CAS  PubMed  Google Scholar 

  • Herder C, Lankisch M, Ziegler D, Rathmann W, Koenig W, Illig T, Doring A, Thorand B, Holle R, Giani G, Martin S, Meisinger C (2009) Subclinical inflammation and diabetic polyneuropathy: MONICA/KORA survey F3 (Augsburg, Germany). Diabetes Care 32:680–682

    PubMed  PubMed Central  Google Scholar 

  • Holmquist L, Stuchbury G, Berbaum K, Muscat S, Young S, Hager K, Engel J, Munch G (2007) Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol Ther 113:154–164

    CAS  PubMed  Google Scholar 

  • Iadecola C, Zhang F, Xu S, Casey R, Ross ME (1995) Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab 15:378–384

    CAS  PubMed  Google Scholar 

  • Jarrett SG, Milder JB, Liang LP, Patel M (2008) The ketogenic diet increases mitochondrial glutathione levels. J Neurochem 106:1044–1051

    CAS  PubMed  Google Scholar 

  • Jiang N, Moyle M, Soule HR, Rote WE, Chopp M (1995) Neutrophil inhibitory factor is neuroprotective after focal ischemia in rats. Ann Neurol 38:935–942

    CAS  PubMed  Google Scholar 

  • Kim JS, Gautam SC, Chopp M, Zaloga C, Jones ML, Ward PA, Welch KM (1995) Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. J Neuroimmunol 56:127–134

    CAS  PubMed  Google Scholar 

  • Kim HJ, Cho EH, Yoo JH, Kim PK, Shin JS, Kim MR, Kim CW (2007) Proteome analysis of serum from type 2 diabetics with nephropathy. J Proteome Res 6:735–743

    CAS  PubMed  Google Scholar 

  • Konrad D, Somwar R, Sweeney G, Yaworsky K, Hayashi M, Ramlal T, Klip A (2001) The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 50:1464–1471

    CAS  PubMed  Google Scholar 

  • Koprowski H, Zheng YM, Heber-Katz E, Fraser N, Rorke L, Fu ZF, Hanlon C, Dietzschold B (1993) In vivo expression of inducible nitric oxide synthase in experimentally induced neurologic diseases. Proc Natl Acad Sci USA 90:3024–3027

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krendel DA, Costigan DA, Hopkins LC (1995) Successful treatment of neuropathies in patients with diabetes mellitus. Arch Neurol 52:1053–1061

    CAS  PubMed  Google Scholar 

  • Kunt T, Forst T, Wilhelm A, Tritschler H, Pfuetzner A, Harzer O, Engelbach M, Zschaebitz A, Stofft E, Beyer J (1999) Alpha-lipoic acid reduces expression of vascular cell adhesion molecule-1 and endothelial adhesion of human monocytes after stimulation with advanced glycation end products. Clin Sci (Lond) 96:75–82

    CAS  Google Scholar 

  • Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97

    PubMed  PubMed Central  Google Scholar 

  • LeVine SM (1992) The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Med Hypotheses 39:271–274

    CAS  PubMed  Google Scholar 

  • Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568

    CAS  PubMed  Google Scholar 

  • Lovell MA, Xie C, Xiong S, Markesbery WR (2003) Protection against amyloid beta peptide and iron/hydrogen peroxide toxicity by alpha lipoic acid. J Alzheimers Dis 5:229–239

    CAS  PubMed  Google Scholar 

  • Marracci GH, Jones RE, McKeon GP, Bourdette DN (2002) Alpha lipoic acid inhibits T cell migration into the spinal cord and suppresses and treats experimental autoimmune encephalomyelitis. J Neuroimmunol 131:104–114

    CAS  PubMed  Google Scholar 

  • Marracci GH, Marquardt WE, Strehlow A, McKeon GP, Gross J, Buck DC, Kozell LB, Bourdette DN (2006) Lipoic acid downmodulates CD4 from human T lymphocytes by dissociation of p56(Lck). Biochem Biophys Res Commun 344:963–971

    CAS  PubMed  Google Scholar 

  • Matsuo Y, Onodera H, Shiga Y, Nakamura M, Ninomiya M, Kihara T, Kogure K (1994) Correlation between myeloperoxidase-quantified neutrophil accumulation and ischemic brain injury in the rat. Effects of neutrophil depletion. Stroke 25:1469–1475

    CAS  PubMed  Google Scholar 

  • Merz PA, Wisniewski HM, Somerville RA, Bobin SA, Masters CL, Iqbal K (1983) Ultrastructural morphology of amyloid fibrils from neuritic and amyloid plaques. Acta Neuropathol 60:113–124

    CAS  PubMed  Google Scholar 

  • Militao GC, Ferreira PM, de Freitas RM (2010) Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures. Neurochem Int 56:16–20

    CAS  PubMed  Google Scholar 

  • Minagar A, Alexander JS (2003) Blood–brain barrier disruption in multiple sclerosis. Mult Scler 9:540–549

    CAS  PubMed  Google Scholar 

  • Montine TJ, Beal MF, Cudkowicz ME, O’Donnell H, Margolin RA, McFarland L, Bachrach AF, Zackert WE, Roberts LJ, Morrow JD (1999) Increased CSF F2-isoprostane concentration in probable AD. Neurology 52:562–565

    CAS  PubMed  Google Scholar 

  • Mori E, del Zoppo GJ, Chambers JD, Copeland BR, Arfors KE (1992) Inhibition of polymorphonuclear leukocyte adherence suppresses no-reflow after focal cerebral ischemia in baboons. Stroke 23:712–718

    CAS  PubMed  Google Scholar 

  • Morini M, Roccatagliata L, Dell’Eva R, Pedemonte E, Furlan R, Minghelli S, Giunti D, Pfeffer U, Marchese M, Noonan D, Mancardi G, Albini A, Uccelli A (2004) Alpha-lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis. J Neuroimmunol 148:146–153

    CAS  PubMed  Google Scholar 

  • Morrissey SP, Le Page E, Edan G (2005) Mitoxantrone in the treatment of multiple sclerosis. Int MS J 12:74–87

    CAS  PubMed  Google Scholar 

  • Nagamatsu M, Nickander KK, Schmelzer JD, Raya A, Wittrock DA, Tritschler H, Low PA (1995) Lipoic acid improves nerve blood flow, reduces oxidative stress, and improves distal nerve conduction in experimental diabetic neuropathy. Diabetes Care 18:1160–1167

    CAS  PubMed  Google Scholar 

  • Negi G, Kumar A, Joshi RP, Sharma SS (2011) Oxidative stress and Nrf2 in the pathophysiology of diabetic neuropathy: old perspective with a new angle. Biochem Biophys Res Commun 408:1–5

    CAS  PubMed  Google Scholar 

  • Nickander KK, McPhee BR, Low PA, Tritschler H (1996) Alpha-lipoic acid: antioxidant potency against lipid peroxidation of neural tissues in vitro and implications for diabetic neuropathy. Free Radic Biol Med 21:631–639

    CAS  PubMed  Google Scholar 

  • Ozkara C, Vigevano F (2011) Immuno- and antiinflammatory therapies in epileptic disorders. Epilepsia 52(3):45–51

    PubMed  Google Scholar 

  • Panigrahi M, Sadguna Y, Shivakumar BR, Kolluri SV, Roy S, Packer L, Ravindranath V (1996) Alpha-lipoic acid protects against reperfusion injury following cerebral ischemia in rats. Brain Res 717:184–188

    CAS  PubMed  Google Scholar 

  • Parry R (1983) Biosynthesis of some sulfur-containing natural products investigations of the mechanism of carbon-sulfur bond formation. Tetrahedron 39:1215–1238

    CAS  Google Scholar 

  • Patrick L (2002) Mercury toxicity and antioxidants: part 1: role of glutathione and alpha-lipoic acid in the treatment of mercury toxicity. Altern Med Rev 7:456–471

    PubMed  Google Scholar 

  • Prasad C, Rupar T, Prasad AN (2011) Pyruvate dehydrogenase deficiency and epilepsy. Brain Dev 33:856–865

    PubMed  Google Scholar 

  • Quinn JF, Bussiere JR, Hammond RS, Montine TJ, Henson E, Jones RE, Stackman RW Jr (2007) Chronic dietary alpha-lipoic acid reduces deficits in hippocampal memory of aged Tg2576 mice. Neurobiol Aging 28:213–225

    CAS  PubMed  Google Scholar 

  • Reljanovic M, Reichel G, Rett K, Lobisch M, Schuette K, Moller W, Tritschler HJ, Mehnert H (1999) Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): a two year multicenter randomized double-blind placebo-controlled trial (ALADIN II). Alpha lipoic acid in diabetic neuropathy. Free Radic Res 31:171–179

    CAS  PubMed  Google Scholar 

  • Richard MJ, Connell BJ, Khan BV, Saleh TM (2011) Cellular mechanisms by which lipoic acid confers protection during the early stages of cerebral ischemia: a possible role for calcium. Neurosci Res 69:299–307

    CAS  PubMed  Google Scholar 

  • Rubanyi GM (1988) Vascular effects of oxygen-derived free radicals. Free Radic Biol Med 4:107–120

    CAS  PubMed  Google Scholar 

  • Rudich A, Tirosh A, Potashnik R, Khamaisi M, Bashan N (1999) Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3 T3-L1 adipocytes. Diabetologia 42:949–957

    CAS  PubMed  Google Scholar 

  • Ruggieri M, Avolio C, Livrea P, Trojano M (2007) Glatiramer acetate in multiple sclerosis: a review. CNS Drug Rev 13:178–191

    CAS  PubMed  Google Scholar 

  • Ruhnau KJ, Meissner HP, Finn JR, Reljanovic M, Lobisch M, Schutte K, Nehrdich D, Tritschler HJ, Mehnert H, Ziegler D (1999) Effects of 3-week oral treatment with the antioxidant thioctic acid (alpha-lipoic acid) in symptomatic diabetic polyneuropathy. Diabet Med 16:1040–1043

    CAS  PubMed  Google Scholar 

  • Russell JW, Golovoy D, Vincent AM, Mahendru P, Olzmann JA, Mentzer A, Feldman EL (2002) High glucose-induced oxidative stress and mitochondrial dysfunction in neurons. FASEB J 16:1738–1748

    CAS  PubMed  Google Scholar 

  • Sachse G, Willms B (1980) Efficacy of thioctic acid in the therapy of peripheral diabetic neuropathy. Horm Metab Res 9:105–107

    CAS  Google Scholar 

  • Said G (2006) Inflammation in diabetic neuropathies. Eur Neurol Dis 6:73–76

    Google Scholar 

  • Said G, Lacroix C, Lozeron P, Ropert A, Plante V, Adams D (2003) Inflammatory vasculopathy in multifocal diabetic neuropathy. Brain 126:376–385

    PubMed  Google Scholar 

  • Salinthone S, Schillace RV, Marracci GH, Bourdette DN, Carr DW (2008a) Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells. J Neuroimmunol 199:46–55

    CAS  PubMed  PubMed Central  Google Scholar 

  • Salinthone S, Yadav V, Bourdette DN, Carr DW (2008b) Lipoic acid: a novel therapeutic approach for multiple sclerosis and other chronic inflammatory diseases of the CNS. Endocr Metab Immune Disord Drug Targets 8:132–142

    CAS  PubMed  Google Scholar 

  • Salinthone S, Yadav V, Schillace RV, Bourdette DN, Carr DW (2010) Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PLoS One 5

    Google Scholar 

  • Santos IM, Tome Ada R, Feitosa CM, de Souza GF, Feng D, de Freitas RM, Jordan J (2010) Lipoic acid blocks seizures induced by pilocarpine via increases in delta-aminolevulinic dehydratase and Na+, K+ −ATPase activity in rat brain. Pharmacol Biochem Behav 95:88–91

    CAS  PubMed  Google Scholar 

  • Santos PS, Costa JP, Tome Ada R, Saldanha GB, de Souza GF, Feng D, de Freitas RM (2011) Oxidative stress in rat striatum after pilocarpine-induced seizures is diminished by alpha-tocopherol. Eur J Pharmacol 668:65–71

    PubMed  Google Scholar 

  • Schreibelt G, Musters RJ, Reijerkerk A, de Groot LR, van der Pol SM, Hendrikx EM, Dopp ED, Dijkstra CD, Drukarch B, de Vries HE (2006) Lipoic acid affects cellular migration into the central nervous system and stabilizes blood–brain barrier integrity. J Immunol 177:2630–2637

    CAS  PubMed  Google Scholar 

  • Shaw JE, Zimmet PZ, de Courten M, Dowse GK, Chitson P, Gareeboo H, Hemraj F, Fareed D, Tuomilehto J, Alberti KG (1999) Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius? Diabetes Care 22:399–402

    CAS  PubMed  Google Scholar 

  • Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM (2009) Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential. Biochim Biophys Acta 1790:1149–1160

    CAS  PubMed  PubMed Central  Google Scholar 

  • Skalska S, Kucera P, Goldenberg Z, Stefek M, Kyselova Z, Jariabka P, Gajdosikova A, Klobucnikova K, Traubner P, Stolc S (2010) Neuropathy in a rat model of mild diabetes induced by multiple low doses of streptozotocin: effects of the antioxidant stobadine in comparison with a high-dose alpha-lipoic acid treatment. Gen Physiol Biophys 29:50–58

    CAS  PubMed  Google Scholar 

  • Smith AR, Shenvi SV, Widlansky M, Suh JH, Hagen TM (2004) Lipoic acid as a potential therapy for chronic diseases associated with oxidative stress. Curr Med Chem 11:1135–1146

    CAS  PubMed  Google Scholar 

  • Soriano SG, Amaravadi LS, Wang YF, Zhou H, Yu GX, Tonra JR, Fairchild-Huntress V, Fang Q, Dunmore JH, Huszar D, Pan Y (2002) Mice deficient in fractalkine are less susceptible to cerebral ischemia-reperfusion injury. J Neuroimmunol 125:59–65

    CAS  PubMed  Google Scholar 

  • Suh JH, Moreau R, Heath SH, Hagen TM (2005) Dietary supplementation with (R)-alpha-lipoic acid reverses the age-related accumulation of iron and depletion of antioxidants in the rat cerebral cortex. Redox Rep 10:52–60

    CAS  PubMed  Google Scholar 

  • Suzuki YJ, Aggarwal BB, Packer L (1992) Alpha-lipoic acid is a potent inhibitor of NF-kappa B activation in human T cells. Biochem Biophys Res Commun 189:1709–1715

    CAS  PubMed  Google Scholar 

  • Suzuki H, Hayashi T, Tojo SJ, Kitagawa H, Kimura K, Mizugaki M, Itoyama Y, Abe K (1999) Anti-P-selectin antibody attenuates rat brain ischemic injury. Neurosci Lett 265:163–166

    CAS  PubMed  Google Scholar 

  • Tarkowski E, Ringqvist A, Rosengren L, Jensen C, Ekholm S, Wennmalm A (2000) Intrathecal release of nitric oxide and its relation to final brain damage in patients with stroke. Cerebrovasc Dis 10:200–206

    CAS  PubMed  Google Scholar 

  • Tauskela JS, Morley P (2004) On the role of Ca2+ in cerebral ischemic preconditioning. Cell Calcium 36:313–322

    CAS  PubMed  Google Scholar 

  • van der Goes A, Brouwer J, Hoekstra K, Roos D, van den Berg TK, Dijkstra CD (1998) Reactive oxygen species are required for the phagocytosis of myelin by macrophages. J Neuroimmunol 92:67–75

    PubMed  Google Scholar 

  • Vezzani A, Granata T (2005) Brain inflammation in epilepsy: experimental and clinical evidence. Epilepsia 46:1724–1743

    CAS  PubMed  Google Scholar 

  • Vezzani A, Conti M, De Luigi A, Ravizza T, Moneta D, Marchesi F, De Simoni MG (1999) Interleukin-1beta immunoreactivity and microglia are enhanced in the rat hippocampus by focal kainate application: functional evidence for enhancement of electrographic seizures. J Neurosci 19:5054–5065

    CAS  PubMed  Google Scholar 

  • Victor M, Ropper AH (2001) Adams & Victor’s principles of neurology, 7th edn. McGraw-Hill, New York

    Google Scholar 

  • Viita H, Sen CK, Roy S, Siljamaki T, Nikkari T, Yla-Herttuala S (1999) High expression of human 15-lipoxygenase induces NF-kappaB-mediated expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and T-cell adhesion on human endothelial cells. Antioxid Redox Signal 1:83–96

    CAS  PubMed  Google Scholar 

  • Vincent AM, Callaghan BC, Smith AL, Feldman EL (2011) Diabetic neuropathy: cellular mechanisms as therapeutic targets. Nat Rev Neurol 7:573–583

    CAS  PubMed  Google Scholar 

  • Vinik AI, Park TS, Stansberry KB, Pittenger GL (2000) Diabetic neuropathies. Diabetologia 43:957–973

    CAS  PubMed  Google Scholar 

  • Wenk GL (2003) Neuropathologic changes in Alzheimer’s disease. J Clin Psychiatry 64(9):7–10

    PubMed  Google Scholar 

  • Wenk GL (2006) Neuropathologic changes in Alzheimer’s disease: potential targets for treatment. J Clin Psychiatry 67(3):3–7; quiz 23

    CAS  PubMed  Google Scholar 

  • Wexler ID, Hemalatha SG, McConnell J, Buist NR, Dahl HH, Berry SA, Cederbaum SD, Patel MS, Kerr DS (1997) Outcome of pyruvate dehydrogenase deficiency treated with ketogenic diets. Studies in patients with identical mutations. Neurology 49:1655–1661

    CAS  PubMed  Google Scholar 

  • Whiteman M, Tritschler H, Halliwell B (1996) Protection against peroxynitrite-dependent tyrosine nitration and alpha 1-antiproteinase inactivation by oxidized and reduced lipoic acid. FEBS Lett 379:74–76

    CAS  PubMed  Google Scholar 

  • Winblad B, Mobius HJ, Stoffler A (2002) Glutamate receptors as a target for Alzheimer’s disease–are clinical results supporting the hope? J Neural Transm Suppl 62:217–225

    CAS  PubMed  Google Scholar 

  • Winiarska K, Malinska D, Szymanski K, Dudziak M, Bryla J (2007) Lipoic acid ameliorates oxidative stress and renal injury in alloxan diabetic rabbits. Biochimie 90:450–459

    PubMed  Google Scholar 

  • Wolinsky JS (2006) The use of glatiramer acetate in the treatment of multiple sclerosis. Adv Neurol 98:273–292

    PubMed  Google Scholar 

  • Wolz P, Krieglstein J (1996) Neuroprotective effects of alpha-lipoic acid and its enantiomers demonstrated in rodent models of focal cerebral ischemia. Neuropharmacology 35:369–375

    CAS  PubMed  Google Scholar 

  • Wong MC, Chung JW, Wong TK (2007) Effects of treatments for symptoms of painful diabetic neuropathy: systematic review. BMJ 335:87

    CAS  PubMed  PubMed Central  Google Scholar 

  • Woo JH, Kim YH, Choi YJ, Kim DG, Lee KS, Bae JH, Min DS, Chang JS, Jeong YJ, Lee YH, Park JW, Kwon TK (2003) Molecular mechanisms of curcumin-induced cytotoxicity: induction of apoptosis through generation of reactive oxygen species, down-regulation of Bcl-XL and IAP, the release of cytochrome c and inhibition of Akt. Carcinogenesis 24:1199–1208

    CAS  PubMed  Google Scholar 

  • Xu K, Stringer JL (2008) Antioxidants and free radical scavengers do not consistently delay seizure onset in animal models of acute seizures. Epilepsy Behav 13:77–82

    PubMed  PubMed Central  Google Scholar 

  • Yadav V, Marracci G, Lovera J, Woodward W, Bogardus K, Marquardt W, Shinto L, Morris C, Bourdette D (2005) Lipoic acid in multiple sclerosis: a pilot study. Mult Scler 11:159–165

    CAS  PubMed  Google Scholar 

  • Zhang WJ, Frei B (2001) Alpha-lipoic acid inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in human aortic endothelial cells. FASEB J 15:2423–2432

    CAS  PubMed  Google Scholar 

  • Zhang RL, Chopp M, Li Y, Zaloga C, Jiang N, Jones ML, Miyasaka M, Ward PA (1994) Anti-ICAM-1 antibody reduces ischemic cell damage after transient middle cerebral artery occlusion in the rat. Neurology 44:1747–1751

    CAS  PubMed  Google Scholar 

  • Zhang WJ, Wei H, Hagen T, Frei B (2007) Alpha-lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway. Proc Natl Acad Sci USA 104:4077–4082

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ziegler D, Hanefeld M, Ruhnau KJ, Meissner HP, Lobisch M, Schutte K, Gries FA (1995) Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant alpha-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN study). Diabetologia 38:1425–1433

    CAS  PubMed  Google Scholar 

  • Ziegler D, Hanefeld M, Ruhnau KJ, Hasche H, Lobisch M, Schutte K, Kerum G, Malessa R (1999a) Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III study). ALADIN III study group. Alpha-lipoic acid in diabetic neuropathy. Diabetes Care 22:1296–1301

    CAS  PubMed  Google Scholar 

  • Ziegler D, Reljanovic M, Mehnert H, Gries FA (1999b) Alpha-lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials. Exp Clin Endocrinol Diabetes 107:421–430

    CAS  PubMed  Google Scholar 

  • Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, Munzel U, Yakhno N, Raz I, Novosadova M, Maus J, Samigullin R (2006) Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care 29:2365–2370

    CAS  PubMed  Google Scholar 

  • Ziegler D, Low PA, Litchy WJ, Boulton AJ, Vinik AI, Freeman R, Samigullin R, Tritschler H, Munzel U, Maus J, Schutte K, Dyck PJ (2011) Efficacy and safety of antioxidant treatment with {alpha}-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care 34:2054–2060

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This research was supported by Merit Award and Career Development Award from the Department of Veterans Affairs, Biomedical Laboratory Research & Development Service (DWC and SS). These funding sources had no involvement in study design, collection, analysis and interpretation of data, in the writing of the manuscript, or in the decision to submit the article for publication.

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Authors and Affiliations

  1. Portland Veterans Affairs Medical Center and Department of Endocrinology, Oregon Health & Science University, VAMC RD-8 3710 US Veterans Hospital Road, Portland, OR, 97239, USA

    Daniel W. Carr & Sonemany Salinthone

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  1. Daniel W. Carr
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  2. Sonemany Salinthone
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Correspondence to Daniel W. Carr .

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Editors and Affiliations

  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Carr, D.W., Salinthone, S. (2014). Lipoic Acid, Inflammation and Diseases of the Nervous System. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_86

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