Genes involved in hereditary ataxias

Trends Neurosci. 1998 Sep;21(9):413-8. doi: 10.1016/s0166-2236(98)01315-0.

Abstract

The hereditary ataxias are a group of inherited neurodegenerative disorders characterized by progressive ataxia that results from degeneration of the cerebellum and its afferent and efferent connections. Recent molecular research has led not only to the discovery of a number of causative mutations, but also shed light on the likely mechanisms by which these mutations cause the respective phenotypes. In Friedreich's ataxia (FRDA), the most common type of autosomal recessive ataxia, the loss of a mitochondrial protein, frataxin, results in overload of mitochondrial iron and oxidative stress. The autosomal dominant ataxias, spinocerebellar ataxia type I (SCAI), SCA2, SCA3 and SCA7, are caused by inheritance of an unstable, expanded CAG trinucleotide repeat. These disorders are assumed to be due to a novel deleterious function of the extended polyglutamine sequences within the proteins encoded by the respective genes. Recent observations in transgenic mice and in human post-mortem tissue suggest that the extended proteins are transported into the nucleus of neurons where they form intranuclear inclusions that disrupt normal nuclear function. In another group of dominant disorders, episodic ataxia type I and type 2 (EA-I, EA-2) and SCA6, the mutations affect genes that code for ion channels.

Publication types

  • Review

MeSH terms

  • Animals
  • Ataxin-1
  • Ataxins
  • Brain Chemistry / genetics
  • Cerebellum / chemistry*
  • Frataxin
  • Friedreich Ataxia / genetics*
  • Gene Deletion
  • Humans
  • Iron-Binding Proteins*
  • Mutation, Missense
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Trinucleotide Repeats

Substances

  • ATXN1 protein, human
  • Ataxin-1
  • Ataxins
  • Atxn1 protein, mouse
  • Iron-Binding Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Phosphotransferases (Alcohol Group Acceptor)