Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential

Alpha-lipoic acid as a biological antioxidant

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Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants

Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947 · see citing works

Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex

Zhang, D. D., Lo, S., Cross, J. V., Templeton, D. J., & Hannink, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.24.10941-10953.2004 · Cited by 1,262 · see citing works

Phosphorylation of Nrf2 at Ser-40 by Protein Kinase C Regulates Antioxidant Response Element-mediated Transcription*

Huang, H.-C., Nguyen, T., & Pickett, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206911200 · Cited by 1,070 · see citing works

Reversible Inactivation of the Tumor Suppressor PTEN by H2O2

Lee, S.-R., Yang, K., Kwon, J., Lee, C., Jeong, W., & Rhee, S. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111899200 · Cited by 1,061 · see citing works

Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor

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Oxidative and Electrophilic Stresses Activate Nrf2 through Inhibition of Ubiquitination Activity of Keap1

Kobayashi, A., Kang, M.-I., Watai, Y., Tong, K. I., Shibata, T., Uchida, K., & Yamamoto, M. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.221-229.2006 · Cited by 933 · see citing works

The pharmacology of the antioxidant lipoic acid

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Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid

Suh, J. H., Shenvi, S. V., Dixon, B. M., Liu, H., Jaiswal, A. K., Liu, R.-M., & Hagen, T. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400282101 · Cited by 774 · see citing works

Multienzyme complexes

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Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy

Ziegler, D., As, A., Николаевич, Б. А., Dyck, P. J. B., Владимировна, Г. И., Low, P. A., Munzel, U., Yakhno, N. N., Raz, I., Novosadova, M., et al. (2006) · Diabetes Care · doi:10.2337/dc06-1216 · Cited by 563 · see citing works

Molecular aspects of lipoic acid in the prevention of diabetes complications

Packer, L., Kraemer, K., & Rimbach, G. (2001) · Nutrition · doi:10.1016/s0899-9007(01)00658-x · Cited by 556 · see citing works

A Molecular Basis for Insulin Resistance

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Treatment of symptomatic diabetic polyneuropathy with the antioxidant α‐lipoic acid: a meta‐analysis

Ziegler, D., Nowak, H., Kempler, P., Vargha, P., & Low, P. A. (2004) · Diabetic Medicine · doi:10.1111/j.1464-5491.2004.01109.x · Cited by 549 · see citing works

Regulation of the antioxidant response element by protein kinase C-mediated phosphorylation of NF-E2-related factor 2

Huang, H.-C., Nguyen, T., & Pickett, C. B. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220418997 · Cited by 539 · see citing works

Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant ?-lipoic acid: A 3-week multicentre randomized controlled trial (ALADIN Study)

Ziegler, D., Hanefeld, M., Ruhnau, K. J., Mei\ner, H. P., Lobisch, M., Sch�tte, K., Gries, F. A., & The ALADIN Study Group (1995) · Diabetologia · doi:10.1007/bf00400603 · Cited by 525 · see citing works

Phosphorylation of Nrf2 at Ser40 by Protein Kinase C in Response to Antioxidants Leads to the Release of Nrf2 from INrf2, but Is Not Required for Nrf2 Stabilization/Accumulation in the Nucleus and Transcriptional Activation of Antioxidant Response Element-mediated NAD(P)H:Quinone Oxidoreductase-1 Gene Expression

Bloom, D. A., & Jaiswal, A. K. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307633200 · Cited by 523 · see citing works

Anti-obesity effects of α-lipoic acid mediated by suppression of hypothalamic AMP-activated protein kinase

Kim, M., Park, J., NamKoong, C., Jang, P., Ryu, J., Song, H.-S., Yun, J.-Y., Nam‐Goong, I. S., Ha, J., Park, I.-S., et al. (2004) · Nature Medicine · doi:10.1038/nm1061 · Cited by 522 · see citing works

Physiological Significance of Reactive Cysteine Residues of Keap1 in Determining Nrf2 Activity

Yamamoto, T., Suzuki, T., Kobayashi, A., Wakabayashi, J., Maher, J. M., Motohashi, H., & Yamamoto, M. P. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01704-07 · Cited by 515 · see citing works

Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: Partial reversal by feeding acetyl- l -carnitine and/or R -α-lipoic acid

Liu, J., Head, E., Gharib, A., Yuan, W., Ingersoll, R. T., Hagen, T. M., Cotman, C. W., & Ames, B. N. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.261709299 · Cited by 504 · see citing works

Lipoic Acid as a Potential Therapy for Chronic Diseases Associated with Oxidative Stress

Smith, A. R. W., Shenvi, S. V., Widlansky, M. E., Suh, J.-I., & Hagen, T. M. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043365387 · Cited by 461 · see citing works

Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2

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The antioxidants α‐lipoic acid and <i>N</i> ‐acetylcysteine reverse memory impairment and brain oxidative stress in aged SAMP8 mice

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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.

Ziegler, D., Markolf Hanefeld, E., Ruhnau, K., Hasche, H., Lobisch, M., Schütte, K., Kerum, G., & Malessa, R. (1999) · Diabetes Care · doi:10.2337/diacare.22.8.1296 · Cited by 432 · see citing works

Insulin-Dependent Activation of Endothelial Nitric Oxide Synthase Is Impaired by O-Linked Glycosylation Modification of Signaling Proteins in Human Coronary Endothelial Cells

Federici, M., Menghini, R., Mauriello, A., Hribal, M. L., Ferrelli, F., Lauro, D., Sbraccia, P., Spagnoli, L. G., Sesti, G., & Lauro, R. (2002) · Circulation · doi:10.1161/01.cir.0000023043.02648.51 · Cited by 372 · see citing works

Dihydrolipoic acid—a universal antioxidant both in the membrane and in the aqueous phase

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The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid

The SYDNEY Trial Authors, F. T. S. T. S. G., As, A., Barinov, A., Dyck, P. J. B., Hermann, R., Kozlova, N. A., Litchy, W. J., Low, P. A., Nehrdich, D., Novosadova, M., et al. (2003) · Diabetes Care · doi:10.2337/diacare.26.3.770 · Cited by 359 · see citing works

Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization

Han, D., Handelman, G. J., Marcocci, L., Sen, C. K., Roy, S., Kobuchi, H., Tritschler, H., Flohé, L., & Packer, L. (1997) · BioFactors · doi:10.1002/biof.5520060303 · Cited by 334 · see citing works

Specific Patterns of Electrophile Adduction Trigger Keap1 Ubiquitination and Nrf2 Activation

Hong, F., Sekhar, K. R., Freeman, M. L., & Liebler, D. C. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503346200 · Cited by 316 · see citing works

Contraction signaling to glucose transport in skeletal muscle

Jessen, N., & Goodyear, L. J. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00175.2005 · Cited by 311 · cited 6× · see citing works

Metal complexing agents as therapies for Alzheimer’s disease

Bush, A. I. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00120-3 · Cited by 310 · see citing works

Lipoic and Dihydrolipoic Acids as Antioxidants. a Critical Evaluation

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Exercise increases muscle GLUT-4 levels and insulin action in subjects with impaired glucose tolerance

HUGHES, V. A., FIATARONE, M. A., Fielding, R. A., Kahn, B. B., Ferrara, C. M., Shepherd, P. R., Fisher, E. C., Wolfe, R. R., Elahi, D., & Evans, W. J. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.264.6.e855 · Cited by 300 · see citing works

α‐Lipoic acid inhibits TNF‐a‐induced NF‐κB activation and adhesion molecule expression in human aortic endothelial cells

Zhang, W., & Frei, B. B. (2001) · The FASEB Journal · doi:10.1096/fj.01-0260com · Cited by 300 · see citing works

Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (α-lipoic acid): A two year multicenter randomized double-blind placebo-controlled trial (ALADIN II)

Reljanović, M., Reichel, G., Kristian, R. E. T. T., Lobisch, M., Schütte, K., Möller, W., Tritschler, H., & Mehnert, H. (1999) · Free Radical Research · doi:10.1080/10715769900300721 · Cited by 283 · see citing works

Irbesartan and Lipoic Acid Improve Endothelial Function and Reduce Markers of Inflammation in the Metabolic Syndrome

Sola, S., Mir, M. Q. S., Cheema, F. A., Merchant, N., Menon, R. G., Parthasarathy, S., & Khan, B. V. (2005) · Circulation · doi:10.1161/01.cir.0000153272.48711.b9 · Cited by 281 · see citing works

AMPK-Mediated AS160 Phosphorylation in Skeletal Muscle Is Dependent on AMPK Catalytic and Regulatory Subunits

Treebak, J. T., Glund, S., Deshmukh, A. S., Klein, D. K., Long, Y. C., Jensen, T. E., Jørgensen, S. B., Viollet, B., Andersson, L., Neumann, D., et al. (2006) · Diabetes · doi:10.2337/db06-0175 · Cited by 281 · see citing works

Effects of Treatment With the Antioxidant α-Lipoic Acid on Cardiac Autonomic Neuropathy in NIDDM Patients: A 4-month randomized controlled multicenter trial (DEKAN Study)

Ziegler, D., Schatz, H., Conrad, F., Gries, F. A., Ulrich, H., The DEKAN Study Group, & Reichel, G. (1997) · Diabetes Care · doi:10.2337/diacare.20.3.369 · Cited by 280 · see citing works

Oral administration of rac-α-lipoic acid modulates insulin sensitivity in patients with type-2 diabetes mellitus: a placebo-controlled pilot trial

Jacob, S., Ruus, P., Hermann, R., Tritschler, H. J., Maerker, E., Renn, W., Augustin, H. J., Dietze, G. J., & Rett, K. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00089-1 · Cited by 280 · see citing works

Mechanism of action of isothiocyanates: the induction of ARE-regulated genes is associated with activation of ERK and JNK and the phosphorylation and nuclear translocation of Nrf2

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α-Lipoic acid attenuates LPS-induced inflammatory responses by activating the phosphoinositide 3-kinase/Akt signaling pathway

Zhang, W., Hao, W., Hagen, T. M., & Frei, B. B. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0700305104 · Cited by 258 · see citing works

Thioctic (lipoic) acid: a therapeutic metal-chelating antioxidant?

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5′-AMP-activated Protein Kinase Phosphorylates IRS-1 on Ser-789 in Mouse C2C12 Myotubes in Response to 5-Aminoimidazole-4-carboxamide Riboside

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Thioctic Acid and Dihydrolipoic Acid are Novel Antioxidants Which Interact With Reactive Oxygen Species

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Insulin Receptor Substrate-1 and Phosphoinositide-Dependent Kinase-1 Are Required for Insulin-Stimulated Production of Nitric Oxide in Endothelial Cells

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α-Lipoic acid increases insulin sensitivity by activating AMPK in skeletal muscle

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Cloning and Functional Expression of a cDNA Encoding a Mammalian Sodium-dependent Vitamin Transporter Mediating the Uptake of Pantothenate, Biotin, and Lipoate

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Interplay between lipoic acid and glutathione in the protection against microsomal lipid peroxidation

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The Antihyperglycemic Drug α-Lipoic Acid Stimulates Glucose Uptake via Both GLUT4 Translocation and GLUT4 Activation

Konrad, D., Somwar, R., Sweeney, G., Yaworsky, K., Hayashi, M., Ramlal, T., & Klip, A. (2001) · Diabetes · doi:10.2337/diabetes.50.6.1464 · Cited by 217 · see citing works

α-Lipoic Acid and Cardiovascular Disease

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Covalent Modification at Cys151 Dissociates the Electrophile Sensor Keap1 from the Ubiquitin Ligase CUL3

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Uptake, recycling, and antioxidant actions of α-lipoic acid in endothelial cells

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Stimulation of Glucose Uptake by the Natural Coenzyme α-Lipoic Acid/Thioctic Acid: Participation of Elements of the Insulin Signaling Pathway

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Effect of alpha‐lipoic acid supplementation on markers of protein oxidation in post‐mitotic tissues of ageing rat

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Beneficial effects of α-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress

Heitzer, T. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00551-2 · Cited by 194 · see citing works

alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

Konrad, T., Vicini, P., Kusterer, K., Höflich, A., Assadkhani, A., Böhles, H. J., Sewell, A., Tritschler, H., Cobelli, C., & Usadel, K. H. (1999) · Diabetes Care · doi:10.2337/diacare.22.2.280 · Cited by 189 · see citing works

Lipoic acid: A multifunctional antioxidant

Bast, A., & Haenen, G. R. M. M. (2003) · BioFactors · doi:10.1002/biof.5520170120 · Cited by 184 · see citing works

Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo.

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Role of Akt substrate of 160 kDa in insulin-stimulated and contraction-stimulated glucose transport

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Enhancement of glucose disposal in patients with type 2 diabetes by alpha-lipoic acid.

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The Antioxidant α-Lipoic Acid Enhances Insulin-Stimulated Glucose Metabolism in Insulin-Resistant Rat Skeletal Muscle

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Peroxynitrite Reaction with the Reduced and the Oxidized Forms of Lipoic Acid: New Insights into the Reaction of Peroxynitrite with Thiols

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Effects of 3‐week oral treatment with the antioxidant thioctic acid (α‐lipoic acid) in symptomatic diabetic polyneuropathy

Ruhnau, K., Meißner, H., Finn, J. ‐., Reljanović, M., Lobisch, M., Schütte, K., Nehrdich, D., Tritschler, H., Mehnert, H., & Ziegler, D. (1999) · Diabetic Medicine · doi:10.1046/j.1464-5491.1999.00190.x · Cited by 178 · see citing works

α-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats

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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

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Prevention of Hypertension, Insulin Resistance, and Oxidative Stress by α-Lipoic Acid

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Multiple roles of phosphatidylinositol 3-kinase in regulation of glucose transport, amino acid transport, and glucose transporters in L6 skeletal muscle cells

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Mitochondrial Decay in the Aging Rat Heart

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Lipoic acid in multiple sclerosis: a pilot study

Yadav, V., Marracci, G., Lovera, J. F., Woodward, W. R., Bogardus, K., Marquardt, W. E., Shinto, L. H., Morris, C. D., & BOURDETTE, D. N. (2005) · Multiple Sclerosis Journal · doi:10.1191/1352458505ms1143oa · Cited by 153 · see citing works

(R)-α-Lipoic acid reverses the age-related loss in GSH redox status in post-mitotic tissues: evidence for increased cysteine requirement for GSH synthesis

Suh, J. H., Wang, H., Liu, R.-M., Liu, J., & Hagen, T. M. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.12.020 · Cited by 147 · see citing works

Plasma Kinetics, Metabolism, and Urinary Excretion of Alpha‐Lipoic Acid following Oral Administration in Healthy Volunteers

Teichert, J., Hermann, R. B., Ruus, P., et al. (2003) · The Journal of Clinical Pharmacology · doi:10.1177/0091270003258654 · Cited by 147 · see citing works

Interleukin‐6 and acute coronary syndrome

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Lipoic acid prevents hypertension, hyperglycemia, and the increase in heart mitochondrial superoxide production

Midaoui, A. E. (2003) · American Journal of Hypertension · doi:10.1016/s0895-7061(02)03253-3 · Cited by 144 · see citing works

Age‐associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with ( R )‐α‐lipoic acid supplementation

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α-lipoic acid decreases oxidative stress even in diabetic patients with poor glycemic control and albuminuria

Borcea, V., Nourooz‐Zadeh, J., Wolff, S. P., Klevesath, M. S., Hofmann, M. A., Urich, H., Wahl, P. M., Ziegler, R., Tritschler, H., Halliwell, B. B., et al. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00011-8 · Cited by 141 · see citing works

α-Lipoic Acid Prevents Endothelial Dysfunction in Obese Rats via Activation of AMP-Activated Protein Kinase

Lee, W. J., Lee, I. K., Kim, H. S., Kim, Y., Koh, E. H., Won, J. C., Han, S. M., Kim, M., Jo, I., Oh, G. T., et al. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000190667.33224.4c · Cited by 137 · see citing works

Protection against glutamate-induced cytotoxicity in C6 glial cells by thiol antioxidants

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Engagement of the insulin-sensitive pathway in the stimulation of glucose transport by α-lipoic acid in 3T3-L1 adipocytes

Yaworsky, K., Somwar, R., Ramlal, T., Tritschler, H., & Klip, A. (2000) · Diabetologia · doi:10.1007/s001250050047 · Cited by 134 · see citing works

Oxidative stress in the aging rat heart is reversed by dietary supplementation with ( R )‐α‐lipoic acid

Suh, J. H., Shigeno, E. T., Morrow, J. D., Cox, J., ROCHA, A. E., Frei, B. B., & Hagen, T. M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0176com · Cited by 133 · see citing works

Safety evaluation of α-lipoic acid (ALA)

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α-Lipoic acid is effective in prevention and treatment of experimental autoimmune encephalomyelitis

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