TY - JOUR
T1 - Oxidative Stress and Neuronal Adaptation in Alzheimer Disease
T2 - The Role of SAPK Pathways
AU - Zhu, Xiongwei
AU - Raina, Arun K.
AU - Lee, Hyoung Gon
AU - Chao, Mark
AU - Nunomura, Akihiko
AU - Tabaton, Massimo
AU - Petersen, Robert B.
AU - Perry, George
AU - Smith, Mark A.
PY - 2003/10
Y1 - 2003/10
N2 - Recent evidence indicates that oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the hallmark pathologies, namely neurofibrillary tangles and senile plaques. The interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of reactive oxygen species in diseased neurons. Oxidative damage to major cellular molecules is seen in a number of disease states that are either acute or chronic and it is apparent that without eliciting compensations that restore redox balance, cells will rapidly succumb to death. Indeed, although oxidative stress is a prominent feature in Alzheimer disease, few vulnerable neurons show clear signs of apoptosis, suggesting that the level of oxidative stress does not significantly exceed neuronal oxidative defenses. In light of this observation, we propose that neurons in Alzheimer disease are exposed to low, but chronic, levels of oxidative stress that lead neurons to elicit adaptive responses such as the activation of stress-activated protein kinase pathways.
AB - Recent evidence indicates that oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the hallmark pathologies, namely neurofibrillary tangles and senile plaques. The interaction of abnormal mitochondria, redox transition metals, and oxidative stress response elements contributes to the generation of reactive oxygen species in diseased neurons. Oxidative damage to major cellular molecules is seen in a number of disease states that are either acute or chronic and it is apparent that without eliciting compensations that restore redox balance, cells will rapidly succumb to death. Indeed, although oxidative stress is a prominent feature in Alzheimer disease, few vulnerable neurons show clear signs of apoptosis, suggesting that the level of oxidative stress does not significantly exceed neuronal oxidative defenses. In light of this observation, we propose that neurons in Alzheimer disease are exposed to low, but chronic, levels of oxidative stress that lead neurons to elicit adaptive responses such as the activation of stress-activated protein kinase pathways.
UR - http://www.scopus.com/inward/record.url?scp=0142139355&partnerID=8YFLogxK
U2 - 10.1089/152308603770310220
DO - 10.1089/152308603770310220
M3 - Short survey
C2 - 14580312
AN - SCOPUS:0142139355
VL - 5
SP - 571
EP - 576
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
SN - 1523-0864
IS - 5
ER -