Document Detail


Neuroprotection by the metabolic antioxidant alpha-lipoic acid.
MedLine Citation:
PMID:  8958163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reactive oxygen species are thought to be involved in a number of types of acute and chronic pathologic conditions in the brain and neural tissue. The metabolic antioxidant alpha-lipoate (thioctic acid, 1, 2-dithiolane-3-pentanoic acid; 1, 2-dithiolane-3 valeric acid; and 6, 8-dithiooctanoic acid) is a low molecular weight substance that is absorbed from the diet and crosses the blood-brain barrier. alpha-Lipoate is taken up and reduced in cells and tissues to dihydrolipoate, which is also exported to the extracellular medium; hence, protection is afforded to both intracellular and extracellular environments. Both alpha-lipoate and especially dihydrolipoate have been shown to be potent antioxidants, to regenerate through redox cycling other antioxidants like vitamin C and vitamin E, and to raise intracellular glutathione levels. Thus, it would seem an ideal substance in the treatment of oxidative brain and neural disorders involving free radical processes. Examination of current research reveals protective effects of these compounds in cerebral ischemia-reperfusion, excitotoxic amino acid brain injury, mitochondrial dysfunction, diabetes and diabetic neuropathy, inborn errors of metabolism, and other causes of acute or chronic damage to brain or neural tissue. Very few neuropharmacological intervention strategies are currently available for the treatment of stroke and numerous other brain disorders involving free radical injury. We propose that the various metabolic antioxidant properties of alpha-lipoate relate to its possible therapeutic roles in a variety of brain and neuronal tissue pathologies: thiols are central to antioxidant defense in brain and other tissues. The most important thiol antioxidant, glutathione, cannot be directly administered, whereas alpha-lipoic acid can. In vitro, animal, and preliminary human studies indicate that alpha-lipoate may be effective in numerous neurodegenerative disorders.
Authors:
L Packer; H J Tritschler; K Wessel
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Free radical biology & medicine     Volume:  22     ISSN:  0891-5849     ISO Abbreviation:  Free Radic. Biol. Med.     Publication Date:  1997  
Date Detail:
Created Date:  1997-04-10     Completed Date:  1997-04-10     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8709159     Medline TA:  Free Radic Biol Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  359-78     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3200, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antioxidants / pharmacology*,  therapeutic use
Brain / blood supply,  drug effects*
Humans
Nerve Degeneration / drug effects
Nervous System / drug effects*
Neuroprotective Agents / pharmacology*,  therapeutic use
Oxidative Stress / drug effects
Reperfusion Injury / prevention & control
Thioctic Acid / pharmacology*,  therapeutic use
Chemical
Reg. No./Substance:
0/Antioxidants; 0/Neuroprotective Agents; 62-46-4/Thioctic Acid

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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