Xu Jianjun, Minobe Etsuko, Kameyama Masaki
Department of Physiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.
Front Cell Neurosci. 2022 Apr 14;16:867385. doi: 10.3389/fncel.2022.867385. eCollection 2022.
Parkinson's disease (PD), a common neurodegenerative disease characterized by motor dysfunction, results from the death of dopaminergic neurons in the substantia nigra pars compacta (SNc). Although the precise causes of PD are still unknown, several risk factors for PD have been determined, including aging, genetic mutations, environmental factors, and gender. Currently, the molecular mechanisms underlying risk factor-related neurodegeneration in PD remain elusive. Endoplasmic reticulum stress, excessive reactive oxygen species production, and impaired autophagy have been implicated in neuronal death in the SNc in PD. Considering that these pathological processes are tightly associated with intracellular Ca, it is reasonable to hypothesize that dysregulation of Ca handling may mediate risk factors-related PD pathogenesis. We review the recent findings on how risk factors cause Ca dyshomeostasis and how aberrant Ca handling triggers dopaminergic neurodegeneration in the SNc in PD, thus putting forward the possibility that manipulation of specific Ca handling proteins and subcellular Ca homeostasis may lead to new promising strategies for PD treatment.
帕金森病（PD）是一种以运动功能障碍为特征的常见神经退行性疾病，由黑质致密部（SNc）中多巴胺能神经元的死亡所致。尽管PD的确切病因仍不明，但已确定了几个PD的风险因素，包括衰老、基因突变、环境因素和性别。目前，PD中与风险因素相关的神经退行性变的分子机制仍不清楚。内质网应激、过量活性氧生成和自噬受损与PD中SNc的神经元死亡有关。鉴于这些病理过程与细胞内钙密切相关，合理推测钙处理失调可能介导与风险因素相关的PD发病机制。我们综述了关于风险因素如何导致钙稳态失调以及异常钙处理如何触发PD中SNc多巴胺能神经退行性变的最新研究发现，从而提出操纵特定钙处理蛋白和亚细胞钙稳态可能带来PD治疗新的有前景策略的可能性。
