Function and regulation of Dyrk1A: towards understanding Down syndrome

Cell Mol Life Sci. 2009 Oct;66(20):3235-40. doi: 10.1007/s00018-009-0123-2. Epub 2009 Aug 14.

Abstract

Down syndrome (DS) is associated with a variety of symptoms, such as incapacitating mental retardation and neurodegeneration (i.e., Alzheimer's disease), that prevent patients from leading fully independent lives. These phenotypes are a direct consequence of the overexpression of chromosome 21 genes, which are present in duplicate due to non-disjunction of chromosome 21. Accumulating data suggest that the chromosome 21 gene product, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (Dyrk1A), participates in the pathogenic mechanisms underlying the mental and other physical symptoms of DS. In this review, we summarize the evidence supporting a role for Dyrk1A in DS, especially DS pathogenesis. Recently, several natural and synthetic compounds have been identified as Dyrk1A inhibitors. Understanding the function and regulation of Dyrk1A may lead to the development of novel therapeutic agents aimed at treating DS.

Publication types

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

MeSH terms

  • Animals
  • Chromosomes, Human, Pair 21
  • Disease Models, Animal
  • Down Syndrome / drug therapy
  • Down Syndrome / genetics*
  • Gene Expression Regulation*
  • Humans
  • Mice
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / physiology*

Substances

  • Dyrk kinase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases