Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Laboratory for Developmental Neurobiology, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Biochim Biophys Acta Mol Cell Res. 2018 Nov;1865(11 Pt B):1733-1744. doi: 10.1016/j.bbamcr.2018.05.009. Epub 2018 May 16.
Spinocerebellar ataxia (SCA) is a neural disorder, which is caused by degenerative changes in the cerebellum. SCA is primarily characterized by gait ataxia, and additional clinical features include nystagmus, dysarthria, tremors and cerebellar atrophy. Forty-four hereditary SCAs have been identified to date, along with >35 SCA-associated genes. Despite the great diversity and distinct functionalities of the SCA-related genes, accumulating evidence supports the occurrence of a common pathophysiological event among several hereditary SCAs. Altered calcium (Ca) homeostasis in the Purkinje cells (PCs) of the cerebellum has been proposed as a possible pathological SCA trigger. In support of this, signaling events that are initiated from or lead to aberrant Ca release from the type 1 inositol 1,4,5-trisphosphate receptor (IPR1), which is highly expressed in cerebellar PCs, seem to be closely associated with the pathogenesis of several SCA types. In this review, we summarize the current research on pathological hereditary SCA events, which involve altered Ca homeostasis in PCs, through IPR1 signaling.
脊髓小脑共济失调（SCA）是一种神经疾病，由小脑的退行性变化引起。SCA 的主要特征是步态共济失调，其他临床特征包括眼球震颤、构音障碍、震颤和小脑萎缩。迄今为止，已经确定了 44 种遗传性 SCA，以及 >35 种 SCA 相关基因。尽管 SCA 相关基因具有很大的多样性和不同的功能，但越来越多的证据支持几种遗传性 SCA 中发生共同的病理生理事件。小脑浦肯野细胞（PCs）中钙（Ca）稳态的改变被认为是 SCA 病理触发的一个可能因素。支持这一观点的是，从高度表达于小脑 PCs 的 I 型肌醇 1,4,5-三磷酸受体（IPR1）起始或导致异常 Ca 释放的信号事件，似乎与几种 SCA 类型的发病机制密切相关。在这篇综述中，我们总结了目前关于涉及 PCs 中 Ca 稳态改变的病理性遗传性 SCA 事件的研究，这些事件通过 IPR1 信号发生。
