Premium
Mitochondrial abnormalities: A primary basis for oxidative damage in Alzheimer's disease
Author(s) -
Smith Mark A.,
Hirai Keisuke,
Nunomura Akihiko,
Perry George
Publication year - 1999
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199901)46:1<26::aid-ddr5>3.0.co;2-8
Subject(s) - oxidative stress , presenilin , mitochondrion , oxidative phosphorylation , reactive oxygen species , biology , neurodegeneration , alzheimer's disease , microbiology and biotechnology , disease , biochemistry , neuroscience , medicine
The most striking feature of Alzheimer's disease (AD) is the number of abnormalities affecting essentially every aspect of brain homeostasis. Recent work suggests that increased oxidative stress that damages lipids, proteins, and nucleic acids and results in the accumulation of redox‐active metals may be responsible for the diversity of systems involved. Interestingly, all of the genetic factors, β‐protein precursor, presenilins, and apolipoprotein E, have been linked to reactive oxygen species production or apoptosis, a process intimately associated with oxidative stress. This leaves open the question of why oxidative damage is increased in AD. In studies of mitochondria, we demonstrated increased mitochondrial DNA specifically in vulnerable neurons in cases of AD, suggesting that AD is marked by a fundamental abnormality in neuronal metabolism. Oxidative stress, therefore, seems to be the element linking the multitude of changes in Alzheimer's disease to a fundamental metabolic deficiency. Drug Dev. Res. 46:26–33, 1999. © 1999 Wiley‐Liss, Inc.