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Function and regulation of Dyrk1A: towards understanding Down syndrome

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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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Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grants (R01-2007-000-11910-0 to W.-J.S. and R11-2007-040-01005-0 to K.C.C.) funded by the Ministry of Education, Science and Technology (MEST), a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2008-314-E00180 to W.-J.S.), and the Korea Health 21 R&D Project (A080551 to K.C.C.) funded by the Ministry of Health, Welfare and Family Affairs. This work was also partly supported by KOSEF grant through the National Research Laboratory Program (R04-2007-000-20014-0 to K.C.C.).

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  1. Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seongsan-no 262, Seodaemun-gu, Seoul, 120-749, Republic of Korea

    Joongkyu Park & Kwang Chul Chung

  2. Graduate Program in Neuroscience, Institute for Brain Science and Technology (IBST), Inje University, Gaegeum 2-dong, Busanjin-gu, Busan, 614-735, Republic of Korea

    Woo-Joo Song

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  1. Joongkyu Park
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Park, J., Song, WJ. & Chung, K.C. Function and regulation of Dyrk1A: towards understanding Down syndrome. Cell. Mol. Life Sci. 66, 3235–3240 (2009). https://doi.org/10.1007/s00018-009-0123-2

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