Intracellular Calcium Dysregulation: Implications for Alzheimer's Disease.
Intracellular Calcium Dysregulation: Implications for Alzheimer's Disease.
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DOI：
10.1155/2016/6701324
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发表时间：
2016
影响因子：
--
通讯作者：
Lariccia V
中科院分区：
文献类型：
--
作者：
Magi S;Castaldo P;Macrì ML;Maiolino M;Matteucci A;Bastioli G;Gratteri S;Amoroso S;Lariccia V
阿尔茨海默病（AD）是一种以进行性神经元丢失为特征的神经退行性疾病。AD与淀粉样蛋白前体蛋白的异常加工相关，这导致淀粉样蛋白-β斑块在脑内沉积。与斑块沉积一起，微管相关蛋白tau的过度磷酸化和神经元内神经元缠结的形成是AD脑中典型的神经病理学特征。涉及特定亚细胞区室（如线粒体和内质网（ER））的细胞功能障碍正在成为AD发病机制中的关键参与者，以及氧化应激增加和钙稳态失调。具体而言，细胞内钙稳态失调已被认为是AD神经功能障碍的常见近端原因。钙信号异常被认为是一种主要与细胞内钙库功能障碍有关的现象，它可以发生在神经元和非神经元细胞中。本文综述了AD发病机制的最新研究成果，主要集中在胞浆和线粒体水平钙稳态的调控。
Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by progressive neuronal loss. AD is associated with aberrant processing of the amyloid precursor protein, which leads to the deposition of amyloid-β plaques within the brain. Together with plaques deposition, the hyperphosphorylation of the microtubules associated protein tau and the formation of intraneuronal neurofibrillary tangles are a typical neuropathological feature in AD brains. Cellular dysfunctions involving specific subcellular compartments, such as mitochondria and endoplasmic reticulum (ER), are emerging as crucial players in the pathogenesis of AD, as well as increased oxidative stress and dysregulation of calcium homeostasis. Specifically, dysregulation of intracellular calcium homeostasis has been suggested as a common proximal cause of neural dysfunction in AD. Aberrant calcium signaling has been considered a phenomenon mainly related to the dysfunction of intracellular calcium stores, which can occur in both neuronal and nonneuronal cells. This review reports the most recent findings on cellular mechanisms involved in the pathogenesis of AD, with main focus on the control of calcium homeostasis at both cytosolic and mitochondrial level.