Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways.
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.
Institute of Pathology, Case Western Reserve University, Cleveland, OH, USA. Xxz12@po.cwru.edu
Xiongwei
X
Zhu
Arun K
AK
Raina
Hyoung-Gon
HG
Lee
Mark
M
Chao
Akihiko
A
Nunomura
Massimo
M
Tabaton
Robert B
RB
Petersen
George
G
Perry
Mark A
MA
Smith
D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008670:Metals / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D009474:Neurons / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases
D008670:Metals; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases