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• Title: Glutathione S-Transferase PI *C Allelic Variant Increases Susceptibility for Late-Onset Alzheimer Disease: Association Study and Relationship with Apolipoprotein E [Epsilon]4 Allele (Molecular Diagnostics and Genetics)
• Author : Clinical Chemistry
• Release Date : January 01, 2005
• Genre: Chemistry,Books,Science & Nature,
• Pages : * pages
• Size : 255 KB

Description

Alzheimer disease (AD) [6] exhibits etiologic, pathologic, and clinical heterogeneity (1-3). Except for rare cases of familial autosomal-dominant AD with early onset produced by mutations of presenilin 1 and 2 and (3-amyloid precursor genes, the vast proportion of cases are sporadic with late onset (4). In this last case, a combination of hereditary and environmental factors could be a crucial pathogenesic mechanism (1, 5). Researchers have recently focused on the role of oxidative stress and cell death in AD because its high oxygen uptake and relatively low degree of antioxidant defenses make the central nervous system sensitive to oxidative stress (6-8). Thus, the role of glutathione S-transferase (GST; EC 2.5.1.18) isoenzymes as risk factors for AD could be important; in particular, GSTs detoxify commonly encountered products generated by oxidative damage (9), and reduced GST activity has been reported in multiple brain regions and in ventricular cerebrospinal fluid in short postmortem interval AD patients (10). Relative to their functional role, GSTs belong to a large family of different enzymes that catalyze the S-conjugation of glutathione with a wide variety of electrophilic compounds, including reactive oxygen species and products of cellular metabolism. In the cell, GSTs detoxify secondary oxidation products generated after interaction of reactive oxygen species that escape the first line of defense (superoxide dismutase, catalase, and glutathione peroxidase) with cellular macromolecules such as DNA, lipids, and protein. Because secondary oxidation products represent highly reactive molecules, without adequate detoxification an extended chain reaction will occur that ultimately leads to degradation of cellular components and cell death (11).

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