Presenilins as endoplasmic reticulum calcium leak channels and Alzheimer's disease pathogenesis

作     者：Charlene SUPNET Ilya BEZPROZVANNY 

作者机构：Department of PhysiologyUniversity of Texas Southwestern Medical Center at Dallas 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2011年第54卷第8期

页      面：744-751页

核心收录：

学科分类：1002[医学-临床医学] 100203[医学-老年医学] 10[医学] 

基　　金：supported by the McKnight Neuroscience of Brain Disorders Award and NIH grant R01AG030746 

主　　题：calcium signaling neurodegeneration presenilins Alzheimer's disease gamma-secretase amyloid 

摘      要：Alzheimer disease(AD) is the most common neurodegenerative disorder worldwide and is at present,*** accumulation of toxic amyloid-beta(Aβ) peptide aggregates in AD brain is thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline,an idea that underlies the amyloid hypothesis of AD etiology in both the familal(FAD) and sporadic forms of the *** mutations causing FAD also result in the dysregulation of neuronal calcium(Ca2+) handling and may contribute to AD pathogenesis,an idea termed the calcium hypothesis of *** in presenilin proteins account for majority of FAD *** function as catalytic subunit ofγ-secretase involved in generation of Aβ peptide Recently,we discovered that presenilns function as low-conductance,passive ER Ca2+ leak channels,independent of γ-secretase *** further discovered that many FAD mutations in presenilins result in loss of ER Ca2+ leak function activity and Ca2+ overload in the *** results provided potential explanation for abnormal Ca2+ signaling observed in FAD cells with mutations in *** latest work on studies of ER Ca2+ leak channel function of presenilins and implications of these findings for understanding AD pathogenesis are discussed in this article.