Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease.
Role of endoplasmic reticulum Ca2+ signaling in the pathogenesis of Alzheimer disease.
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DOI：
10.3389/fnmol.2013.00029
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发表时间：
2013
影响因子：
4.8
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Popugaeva E;Bezprozvanny I
阿尔茨海默病（Alzheimer disease，AD）是21世纪世纪的主要威胁，是导致老年痴呆的主要原因。开发有效的预防AD的治疗方法是神经科学研究的首要任务。AD的淀粉样假说是该领域的主导思想，但迄今为止，所有的淀粉样靶向治疗在临床试验中均失败。除了淀粉样蛋白的积累，也有一致的报告异常钙信号在AD神经元。AD神经元表现出增强的胞内钙（Ca 2+）从内质网（ER）释放和减少的钙库操作的Ca 2+内流（SOC）。这些变化主要是由于ER Ca2+超载而发生的。我们认为，细胞内Ca2+稳态的正常化可能是开发有效的疾病修饰疗法的策略。现就AD中ER Ca2+信号通路的变化作一综述。在本综述中讨论的钙通道包括：三磷酸肌醇受体，兰尼碱受体，早老素作为ER钙泄漏通道，和神经元SOC通道。我们讨论了这些通道的功能是如何改变AD和AD发病机制的重要性是导致钙离子信号的变化。
Alzheimer disease (AD) is a major threat of twenty-first century that is responsible for the majority of dementia in the elderly. Development of effective AD-preventing therapies are the top priority tasks for neuroscience research. Amyloid hypothesis of AD is a dominant idea in the field, but so far all amyloid-targeting therapies have failed in clinical trials. In addition to amyloid accumulation, there are consistent reports of abnormal calcium signaling in AD neurons. AD neurons exhibit enhanced intracellular calcium (Ca2+) liberation from the endoplasmic reticulum (ER) and reduced store-operated Ca2+ entry (SOC). These changes occur primarily as a result of ER Ca2+ overload. We argue that normalization of intracellular Ca2+ homeostasis could be a strategy for development of effective disease-modifying therapies. The current review summarizes recent data about changes in ER Ca2+ signaling in AD. Ca2+ channels that are discussed in the current review include: inositol trisphosphate receptors, ryanodine receptors, presenilins as ER Ca2+ leak channels, and neuronal SOC channels. We discuss how function of these channels is altered in AD and how important are resulting Ca2+ signaling changes for AD pathogenesis.
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影响因子：
5.3
作者：
Honarnejad K;Jung CK;Lammich S;Arzberger T;Kretzschmar H;Herms J
通讯作者：
Herms J
DOI：
10.1523/jneurosci.4367-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Demuro A;Parker I
通讯作者：
Parker I
影响因子：
3.7
作者：
Chakroborty S;Briggs C;Miller MB;Goussakov I;Schneider C;Kim J;Wicks J;Richardson JC;Conklin V;Cameransi BG;Stutzmann GE
通讯作者：
Stutzmann GE
影响因子：
6.1
作者：
Emilsson, L;Saetre, P;Jazin, E
通讯作者：
Jazin, E
DOI：
10.1073/pnas.90.2.567
发表时间：
1993-01-15
影响因子：
11.1
作者：
ARISPE, N;ROJAS, E;POLLARD, HB
通讯作者：
POLLARD, HB