Department of Neuroscience, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Department of Neuroscience, Rosalind Franklin University of Medicine and Science, The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL 60064, USA.
Eur J Pharmacol. 2014 Sep 15;739:83-95. doi: 10.1016/j.ejphar.2013.11.012. Epub 2013 Dec 6.
Calcium ions are versatile and universal biological signaling factors that regulate numerous cellular processes ranging from cell fertilization, to neuronal plasticity that underlies learning and memory, to cell death. For these functions to be properly executed, calcium signaling requires precise regulation, and failure of this regulation may tip the scales from a signal for life to a signal for death. Disruptions in calcium channel function can generate complex multi-system disorders collectively referred to as "calciumopathies" that can target essentially any cell type or organ. In this review, we focus on the multifaceted involvement of calcium signaling in the pathophysiology of Alzheimer's disease (AD), and summarize the various therapeutic options currently available to combat this disease. Detailing the series of disappointing AD clinical trial results on cognitive outcomes, we emphasize the urgency to design alternative therapeutic strategies if synaptic and memory functions are to be preserved. One such approach is to target early calcium channelopathies centrally linked to AD pathogenesis.
钙离子是多功能和普遍的生物信号因子，调节着从细胞受精到神经元可塑性（学习和记忆的基础）再到细胞死亡等多种细胞过程。为了正确执行这些功能，钙信号需要精确的调节，而这种调节的失败可能会使信号从生命信号转变为死亡信号。钙通道功能的中断会产生复杂的多系统紊乱，统称为“钙病变”，这些紊乱可以针对基本上任何细胞类型或器官。在这篇综述中，我们重点关注钙信号在阿尔茨海默病（AD）病理生理学中的多方面作用，并总结了目前可用的各种治疗选择来对抗这种疾病。详细介绍了一系列令人失望的 AD 临床试验结果在认知结果方面，我们强调如果要保留突触和记忆功能，就必须设计替代治疗策略。一种这样的方法是针对与 AD 发病机制密切相关的早期钙通道病变。
