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Review
. 2021 Nov 20;12(11):1833.
doi: 10.3390/genes12111833.

Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome

Helin Atas-Ozcan  1 , Véronique Brault  1 , Arnaud Duchon  1 , Yann Herault  1   2
Affiliations
Review

Dyrk1a from Gene Function in Development and Physiology to Dosage Correction across Life Span in Down Syndrome

Helin Atas-Ozcan et al. Genes (Basel). .

Abstract

Down syndrome is the main cause of intellectual disabilities with a large set of comorbidities from developmental origins but also that appeared across life span. Investigation of the genetic overdosage found in Down syndrome, due to the trisomy of human chromosome 21, has pointed to one main driver gene, the Dual-specificity tyrosine-regulated kinase 1A (Dyrk1a). Dyrk1a is a murine homolog of the drosophila minibrain gene. It has been found to be involved in many biological processes during development and in adulthood. Further analysis showed its haploinsufficiency in mental retardation disease 7 and its involvement in Alzheimer's disease. DYRK1A plays a role in major developmental steps of brain development, controlling the proliferation of neural progenitors, the migration of neurons, their dendritogenesis and the function of the synapse. Several strategies targeting the overdosage of DYRK1A in DS with specific kinase inhibitors have showed promising evidence that DS cognitive conditions can be alleviated. Nevertheless, providing conditions for proper temporal treatment and to tackle the neurodevelopmental and the neurodegenerative aspects of DS across life span is still an open question.

Keywords: cognition; learning and memory; mouse model; neurodevelopmental disorder; preclinical trial; trisomy 21.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
DYRK1A involved in various cellular processes during development and throughout the adult lifetime.
See this image and copyright information in PMC

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