The Role of Mitochondrial Calcium Homeostasis in Alzheimer's and Related Diseases.

The Role of Mitochondrial Calcium Homeostasis in Alzheimer's and Related Diseases.
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线粒体钙稳态在阿尔茨海默病及相关疾病中的作用

DOI:
10.3390/ijms21239153
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发表时间:
2020-12-01
影响因子:
5.6
通讯作者:
Norman KR
Norman KR
中科院分区:
生物学2区
文献类型:
--
作者:
Ryan KC;Ashkavand Z;Norman KR

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钙信号传导对于神经元功能至关重要,其失调与神经退行性疾病有关,包括阿尔茨海默病 (AD)。钙信号传导和线粒体功能之间存在密切的相互关系。各种 AD 模型中越来越多的证据表明,钙稳态失调会极大地改变线粒体活性,进而导致神经退行性变。本综述讨论了钙损害 AD 中线粒体功能的潜在致病机制,重点关注钙在内质网 (ER) 与线粒体通讯、线粒体转运、氧化应激和蛋白质稳态中的影响。这篇综述还总结了最近的数据,这些数据强调了探索钙介导的线粒体功能障碍的机制的必要性,同时提出了调节线粒体钙水平以治疗 AD 等神经退行性疾病的潜在目标。
Calcium signaling is essential for neuronal function, and its dysregulation has been implicated across neurodegenerative diseases, including Alzheimer’s disease (AD). A close reciprocal relationship exists between calcium signaling and mitochondrial function. Growing evidence in a variety of AD models indicates that calcium dyshomeostasis drastically alters mitochondrial activity which, in turn, drives neurodegeneration. This review discusses the potential pathogenic mechanisms by which calcium impairs mitochondrial function in AD, focusing on the impact of calcium in endoplasmic reticulum (ER)–mitochondrial communication, mitochondrial transport, oxidative stress, and protein homeostasis. This review also summarizes recent data that highlight the need for exploring the mechanisms underlying calcium-mediated mitochondrial dysfunction while suggesting potential targets for modulating mitochondrial calcium levels to treat neurodegenerative diseases such as AD.
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