Ca 2+ signaling and spinocerebellar ataxia

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.

Abstract

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 (Ca2+) 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 Ca2+ release from the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1), 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 Ca2+ homeostasis in PCs, through IP3R1 signaling.

Keywords: Calcium; Cerebellum; Endoplasmic reticulum; IP(3) receptor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling*
  • Cerebellum / metabolism
  • Cerebellum / physiopathology
  • Disease Susceptibility*
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation
  • Genetic Predisposition to Disease
  • Humans
  • Inositol 1,4,5-Trisphosphate Receptors / genetics
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Mutation
  • Purkinje Cells / metabolism
  • Spinocerebellar Ataxias / etiology*
  • Spinocerebellar Ataxias / metabolism*

Substances

  • Inositol 1,4,5-Trisphosphate Receptors
  • Calcium