Can the calcium hypothesis explain synaptic loss in Alzheimer's disease?

Can the calcium hypothesis explain synaptic loss in Alzheimer's disease?
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DOI:
10.1159/000354778
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发表时间:
2014
期刊:
Neuro-degenerative diseases
影响因子:
--
通讯作者:
Bezprozvanny I
Bezprozvanny I
中科院分区:
其他
文献类型:
--
作者:
Popugaeva E;Bezprozvanny I

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阿尔茨海默病(AD)是由人类寿命增加引起的对现代人类的威胁。尽管对AD病理学的广泛研究超过100年,但没有疾病预防治疗。越来越多的证据表明钙离子(Ca ~(2+))在AD发病机制中的作用。本文的主要目的是了解现代科学是否能够解释AD早期的突触丢失,并讨论Ca ~(2+)假说在其中的作用。基于本实验室和其他实验室的结果,我们提出,家族性AD相关的早老素突变导致内质网钙超载,导致神经元钙库操纵的Ca ~(2+)(nSOC)代偿性下调。入口通道。我们认为,突触nSOC是必要的成熟的突触棘的稳定性,这一途径的功能障碍可能在AD的突触和记忆丧失中发挥重要作用。
Alzheimer’s disease (AD) is the threat of modern humankind that is provoked by increased human lifespan. Despite extensive studies on AD pathology for more than 100 years there are no disease preventing therapies. Growing evidence suggests the role of calcium (Ca2+) in the pathogenesis of AD. The main purpose of the article is to understand whether modern science is able to explain the synapse loss observed in early AD and discuss the role of Ca2+ hypothesis in it. Based on results obtained in our laboratory and others we propose that familial AD-associated mutations in presenilins cause Ca2+ overload of endoplasmic reticulum stores which leads to compensatory downregulation of neuronal store-operated Ca2+ (nSOC) entry pathway. We propose that synaptic nSOC is necessary for stability of mature synaptic spines and that dysfunction of this pathway may play an important role in synaptic and memory loss in AD.
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