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Alpha Lipoic Acid
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Lester Packer, Hans J. Tritschler and Klaus Wessel Department of
Molecular and Cell Biology, University of California, Berkeley, CA
94720-3200 USA 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 extra cellular 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.
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