Transient receptor potential channels in Alzheimer's disease.
Cognitive impairment and emotional disturbances in Alzheimer's disease (AD) result from the degeneration of synapses and neuronal death in the limbic system and associated regions of the cerebral cortex. An alteration in the proteolytic processing of the amyloid precursor protein (APP) results in increased production and accumulation of amyloid beta-peptide (Abeta) in the brain. Abeta can render neurons vulnerable to excitotoxicity and apoptosis by disruption of cellular Ca(2+) homeostasis and neurotoxic factors including reactive oxygen species (ROS), nitric oxide (NO), and cytokines. Many lines of evidence have suggested that transient receptor potential (TRP) channels consisting of six main subfamilies termed the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP (polycystin), TRPML (mucolipin), and TRPA (ankyrin) are involved in Ca(2+) homeostasis disruption. Thus, emerging evidence of the pathophysiological role of TRP channels has yielded promising candidates for molecular entities mediating Ca(2+) homeostasis disruption in AD. In this review, we focus on the TRP channels in AD and highlight some TRP "suspects" for which a role in AD can be anticipated. An understanding of the involvement of TRP channels in AD may lead to the development of new target therapies.
Yamamoto
Shinichiro
S
Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan.
Wajima
Teruaki
T
Hara
Yuji
Y
Nishida
Motohiro
M
Mori
Yasuo
Y
D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D003603:Cytotoxins / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D050051:Transient Receptor Potential Channels / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D003603:Cytotoxins; D018696:Neuroprotective Agents; D050051:Transient Receptor Potential Channels; D002118:Calcium