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Glutathione, Oxidative Stress and Neurodegeneration
Schulz JB, Lindenau J, Seyfried J, & Dichgans J
Eur. J. Biochem. 2000; 267:4904-4911 Feb.
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ABSTRACT
There is significant evidence
that the pathogenesis of several neurodegenerative diseases, including
Parkinson's disease, Alzheimer's disease, Friedreich's ataxia and
amyotrophic lateral sclerosis, may involve the generation of reactive
oxygen species and mitochondrial dysfunction. Here, we review the evidence
for a disturbance of glutathione homeostasis that may either lead to or
result from oxidative stress in neurodegenerative disorders. Glutathione
is an important intracellular antioxidant that protects against a variety
of different antioxidant species. An important role for glutathione was
proposed for the pathogenesis of Parkinson's disease, because a decrease
in total glutathione concentrations in the substantia nigra has been
observed in preclinical stages, at a time at which other biochemical
changes are not yet detectable. Because glutathione does not cross the
blood±brain barrier other treatment options to increase brain
concentrations of glutathione including glutathione analogs, mimetics or
precursors are discussed.
Keywords: Alzheimer's disease; amyotrophic lateral
sclerosis; glutathione; neurodegeneration; Parkinson's disease
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