イシヅカ　ユウタ   Yuta Ishizuka   石塚　佑太    所属   川崎医科大学  医学部 基礎医学　病態代謝学    職種   講師
言語種別	英語
種別	部分執筆
表題	Drebrin in Alzheimer’s Disease
書名	Drebrin
ISBNコード	978-4-431-56548-2
編者名	Tomoaki Shirao, Yuko Sekino
版・巻・頁	pp.203-223
出版社	Springer
出版地 （都市, 国名）	Tokyo
著者・共著者	Yuta Ishizuka*, Kenji Hanamura
発行年月	2017/02/09
概要	Alzheimer's disease (AD) is a neurodegenerative disorder accompanied by severe progressive memory and cognitive impairment. The brain of AD patients has an abundance of two abnormal structures, amyloid plaques (senile plaques) and neurofibrillary tangles. In addition, drebrin loss is another hallmark of AD brains, which is a common feature in the brain of both AD patients and AD mouse models. Strong evidence from human genetics and transgenic mouse models has indicated that amyloid β (Aβ) is part of the etiology and pathogenesis of AD. Recently, it has become clear that synaptic dysfunction, including reduced synaptic transmission and loss of dendritic spines, occurs prior to the formation of amyloid plaques and neuronal cell loss. Furthermore, immunohistochemistry using postmortem human brains and AD mouse models has shown that drebrin loss in postsynaptic sites occurs earlier than the presynaptic change in AD brains. In addition, dysregulation of glutamate receptor trafficking and the p21-activated kinase/LIM kinase pathway has been observed in AD brains. It is now believed that soluble Aβ oligomers, namely, Aβ-derived diffusible ligands (ADDLs), but not insoluble Aβ aggregation mediates Aβ toxicity. ADDLs bind to the postsynaptic site and induce the aberrant morphology and density of dendritic spines. Consistent with the AD mouse models, the surface expression of glutamate receptors decreases after ADDL exposure. Importantly, the ADDL-induced drebrin loss in dendritic spines occurs prior to aberrations in dendritic spine morphology and density. These observations indicate that drebrin loss in dendritic spines occurs at the prodromal stage of AD, before the density and morphology of dendritic spines change. Quantitation of drebrin may be a possible tool for diagnosing the prodromal stage of AD, before dementia development in AD.
AmazonURL	https://www.amazon.co.jp/Drebrin-Structure-Physiological-Pathological-Experimental/dp/4431568174/ref=tmm_pap_swatch_0?_encoding=UTF8&qid=&sr=