Chemistry and biochemistry of oxidative stress in neurodegenerative disease

Citation
Lm. Sayre et al., Chemistry and biochemistry of oxidative stress in neurodegenerative disease, CURR MED CH, 8(7), 2001, pp. 721-738
Citations number
232
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology & Toxicology
Journal title
CURRENT MEDICINAL CHEMISTRY
ISSN journal
0929-8673 → ACNP
Volume
8
Issue
7
Year of publication
2001
Pages
721 - 738
Database
ISI
SICI code
0929-8673(200106)8:7<721:CABOOS>2.0.ZU;2-M
Abstract
The age-related neurodegenerative diseases exemplified by Alzheimer's disea se (AD), Lewy body diseases such as Parkinson's disease (PD), amyotrophic l ateral sclerosis (ALS), and Huntington's disease are characterized by the d eposition of abnormal forms of specific proteins in the brain. Although sev eral Factors appear to underlie the pathological depositions, the cause of neuronal death in each disease appears to be multifactorial. In this regard , evidence in each case for a role of oxidative stress is provided by the f inding that the pathological deposits are immunoreactive to antibodies reco gnizing protein side-chains modified either directly by reactive oxygen or nitrogen species, or by products of lipid peroxidation or glycoxidation. Al though the source(s) of increased oxidative damage are not entirely clear, the findings of increased localization of redox-active transition metals in the brain regions most affected is consistent with their contribution to o xidative stress. It is tempting to speculate that free radical oxygen chemi stry plays a pathogenetic role in all these neurodegenerative conditions, t hough it is as yet undetermined what types of oxidative damage occur early in pathogenesis, and what types are secondary manifestations of dying neuro ns. Delineation of the profile of oxidative damage in each disease will pro vide clues to how the specific neuronal populations are differentially affe cted by the individual disease conditions.