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

Function and regulation of Dyrk1A: towards understanding Down syndrome

Joongkyu Park  1 , Woo-Joo Song, Kwang Chul Chung
Affiliations
Review

Function and regulation of Dyrk1A: towards understanding Down syndrome

Joongkyu Park et al. Cell Mol Life Sci. 2009 Oct.

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.

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Figures

Fig. 1
Fig. 1
Domain structure of Dyrk1A and other Dyrk family members. NLS Nuclear localization signal, KINASE kinase domain, PEST (Pro, Glu, Ser, Thr)-rich domain, His 13-consecutive-histidine repeat, S/T (Ser, Thr)-rich region
Fig. 2
Fig. 2
Substrates and multiple putative roles of Dyrk1A in gene transcription, mRNA splicing, synapse function, and neurodegeneration
See this image and copyright information in PMC

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