Reversal of Calcium Dysregulation as Potential Approach for Treating Alzheimer's Disease.
Reversal of Calcium Dysregulation as Potential Approach for Treating Alzheimer's Disease.
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DOI：
10.2174/1567205017666200528162046
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发表时间：
2020
影响因子：
2.1
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Popugaeva E;Chernyuk D;Bezprozvanny I
尽管数十年的研究和努力，仍然没有有效的阿尔茨海默病（AD）的疾病修饰治疗。近年来的AD临床试验大多以淀粉样蛋白通路为靶点，但均以失败告终。虽然淀粉样蛋白病理是AD的标志和定义特征，但由于疗效低和严重的副作用，靶向淀粉样蛋白途径一直非常具有挑战性。替代的方法或机制，我们的理解的主要原因，记忆丧失的AD需要考虑作为潜在的治疗目标。越来越多的研究表明，AD患者的Ca ~（2+）调节异常在AD的病理过程中起重要作用，并与AD的其他异常如过度炎症、ROS增加、自噬受损、神经退行性变、突触和认知功能障碍等相关。在各种AD模型的背景下，已经报道了胞质空间、内质网（ER）和线粒体中的Ca 2+失调。在临床前模型中，已证明纠正AD中Ca 2+失调的药物或策略作为治疗AD的方法是有前途的。本文就钙离子失调在AD发病中的作用机制及相关病理机制进行综述，并探讨以钙离子失调为靶点开发治疗AD新药的可能途径和策略。
Despite decades of research and effort, there is still no effective disease-modifying treatment for Alzheimer’s Disease (AD). Most of the recent AD clinical trials were targeting amyloid pathway but all these trials failed. Although amyloid pathology is a hallmark and defining feature of AD, targeting amyloid pathway have been very challenging due to low efficacy and serious side effects. Alternative approaches or mechanisms for our understanding of the major cause of memory loss in AD need to be considered as potential therapeutic targets. Increasing studies suggest that Ca2+ dysregulation in AD plays an important role in AD pathology and is associated with other AD abnormalities, such as excessive inflammation, increased ROS, impaired autophagy, neurodegeneration, synapse and cognitive dysfunction. Ca2+ dysregulation in cytosolic space, endoplasmic reticulum (ER) and mitochondria have been reported in the context of various AD models. Drugs or strategies to correct the Ca2+ dysregulation in AD have been demonstrated to be promising as an approach for treatment of AD in preclinical models. This review will discuss the mechanisms of Ca2+ dysregulation in AD and associated pathology, and discuss potential approaches or strategies to develop novel drugs for treatment of AD by targeting Ca2+ dysregulation.
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
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作者：
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