Apoptosis signal regulating kinase 1 (ASK1): potential as a therapeutic target for Alzheimer's disease.
Alzheimer's disease (AD) is the most common form of dementia, characterized by a decline in memory and cognitive function. Clinical manifestations of AD are closely associated with the formation of senile plaques and neurofibrillary tangles, neuronal loss and cognitive decline. Apoptosis signal regulating kinase 1 (ASK1) is a mediator of the MAPK pathway, which regulates various cellular responses such as apoptosis, cell survival, and differentiation. Accumulating evidence indicates that ASK1 plays a key role in the pathogenesis of neurodegenerative disorders such as Huntington's disease and AD. Of particular interest, ASK1 is associated with many signaling pathways, which include endoplasmic reticulum (ER) stress-mediated apoptosis, Aβ-induced neurotoxicity, tau protein phosphorylation, and insulin signal transduction. Here, we review experimental evidence that links ASK1 signaling and AD pathogenesis and propose that ASK1 might be a new point of therapeutic intervention to prevent or treat AD.
Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. sjh1008@yuhs.ac.
Juhyun
J
Song
Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. KAPARK@yuhs.ac.
Kyung Ah
KA
Park
Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. INSKULL@yuhs.ac.
Won Taek
WT
Lee
Department of Anatomy, Yonsei University College of Medicine, Seoul 120-752, Korea. jelee@yuhs.ac.
Jong Eun
JE
Lee
D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D007328:Insulin / Q000378:metabolism; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D018384:Oxidative Stress; D015398:Signal Transduction
D016229:Amyloid beta-Peptides; D007328:Insulin; D048848:MAP Kinase Kinase Kinase 5; C482858:MAP3K5 protein, human