Mutational and biochemical analysis of dopamine in dystonia: Evidence for decreased dopamine D2 receptor inhibition

Richard D. Todd, Joel S. Perlmutter

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

The dystonias are a group of serious movement disorders characterized by involuntary muscle spasms of different parts of the body. We recently proposed that hypofunction of dopamine D2 receptor-mediated inhibition of the indirect output pathway of the basal ganglia can result in dystonia. In this review, we discuss the results of a variety of genetic and biochemical studies in light of this hypothesis. Several forms of early-onset dystonia show distinct autosomal dominant, recessive, or X-linked genetic transmission patterns. Late onset forms of dystonia, though not showing clear Mendelian transmission patterns, also appear to be highly familial. Recently, several genetic-linkage locations have been identified for early-onset dystonia and for two of these loci, mutations decreasing dopamine synthesis have been demonstrated. Biochemical studies of monkeys and man also demonstrate that several types of dystonia occur in a dopamine-deficiency state. Similarly, mice strains developed to be deficient in several dopamine-pathway components have motor abnormalities consistent with dystonia. Hypofunction of the dopamine D2 receptor-mediated inhibition of the indirect output pathway of the putamen may be a common feature of many of these heritable and secondary dystonic syndromes.

Original languageEnglish
Pages (from-to)135-147
Number of pages13
JournalMolecular Neurobiology
Volume16
Issue number2
DOIs
StatePublished - Jan 1 1998

Keywords

  • Dopamine
  • Dopamine receptors
  • Dystonia
  • GTP cyclohydroxylase
  • Putamen
  • Tyrosine hydroxylase

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