Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease.

Therapeutic Strategies to Target Calcium Dysregulation in Alzheimer's Disease.
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DOI:
10.3390/cells9112513
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发表时间:
2020-11-20
期刊:
影响因子:
6
通讯作者:
Bacskai BJ
Bacskai BJ
中科院分区:
生物学2区
文献类型:
--
作者:
Calvo-Rodriguez M;Kharitonova EK;Bacskai BJ

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阿尔茨海默病(AD)是最常见的痴呆症,影响着全球数百万人。不幸的是,目前的治疗方法都不能有效改善AD患者的认知功能,因此,迫切需要开发针对AD早期病因(S)的新疗法。细胞内钙(Ca~(2+))调节对细胞和神经元的正常功能至关重要。已有研究表明,钙离子代谢紊乱是包括AD在内的许多神经退行性疾病的上游因素。因此,旨在靶向或纠正这种钙离子失调的化学试剂或小分子可能作为预防AD发展的治疗策略。此外,神经元并不是唯一表现出钙离子动态平衡失调的细胞,因为在阿尔茨海默病患者大脑中的其他细胞类型中也观察到了钙离子干扰。在这篇综述中,我们研究了参与疾病机制的不同的钙离子通道和隔室,这些可能是AD的潜在靶点。
Alzheimer’s disease (AD) is the most common form of dementia, affecting millions of people worldwide. Unfortunately, none of the current treatments are effective at improving cognitive function in AD patients and, therefore, there is an urgent need for the development of new therapies that target the early cause(s) of AD. Intracellular calcium (Ca2+) regulation is critical for proper cellular and neuronal function. It has been suggested that Ca2+ dyshomeostasis is an upstream factor of many neurodegenerative diseases, including AD. For this reason, chemical agents or small molecules aimed at targeting or correcting this Ca2+ dysregulation might serve as therapeutic strategies to prevent the development of AD. Moreover, neurons are not alone in exhibiting Ca2+ dyshomeostasis, since Ca2+ disruption is observed in other cell types in the brain in AD. In this review, we examine the distinct Ca2+ channels and compartments involved in the disease mechanisms that could be potential targets in AD.
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