Calcium homeostasis, selective vulnerability and Parkinson's disease.
Calcium homeostasis, selective vulnerability and Parkinson's disease.
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DOI：
10.1016/j.tins.2009.01.006
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发表时间：
2009-05
影响因子：
15.9
通讯作者：
Surmeier DJ
中科院分区：
文献类型：
--
作者：
Chan CS;Gertler TS;Surmeier DJ
帕金森病（Parkinson's disease，PD）是一种常见的神经退行性疾病，其核心运动症状可归因于黑质（substantia nigra pars rectuta，SNc）中多巴胺（dopamine，DA）神经元的变性。最近的研究表明，自主起搏过程中L型钙通道的参与使SNc DA神经元对用于创建PD动物模型的线粒体毒素敏感，表明稳态钙应激可能是其选择性脆弱性的决定因素。这一观点得到了线粒体和内质网（目前关于PD起源的理论的关键）在Ca2+稳态中的中心作用的支持。在这里，我们总结了这些证据，并建议这些细胞器的双重作用可能会损害它们的功能，导致SNc DA神经元的加速老化，特别是在面对遗传或环境压力时。最后，我们讨论了减缓PD进展的潜在治疗策略。
Parkinson’s disease (PD) is a common neurodegenerative disorder of which the core motor symptoms are attributable to the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta (SNc). Recent work has revealed that the engagement of L-type Ca2+ channels during autonomous pacemaking renders SNc DA neurons susceptible to mitochondrial toxins used to create animal models of PD, indicating that homeostatic Ca2+ stress could be a determinant of their selective vulnerability. This view is buttressed by the central role of mitochondria and the endoplasmic reticulum (linchpins of current theories about the origins of PD) in Ca2+ homeostasis. Here, we summarize this evidence and suggest the dual roles had by these organelles could compromise their function, leading to accelerated aging of SNc DA neurons, particularly in the face of genetic or environmental stress. We conclude with a discussion of potential therapeutic strategies for slowing the progression of PD.