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Front Behav Neurosci. 2016 Jun 3;10:104. doi: 10.3389/fnbeh.2016.00104. eCollection 2016.

DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome.

Author information

1
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et CellulaireIllkirch, France; UMR7104, Centre National de la Recherche ScientifiqueIllkirch, France; U964, Institut National de la Santé et de la Recherche MédicaleIllkirch, France; Université de StrasbourgIllkirch, France.
2
Department of Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et CellulaireIllkirch, France; UMR7104, Centre National de la Recherche ScientifiqueIllkirch, France; U964, Institut National de la Santé et de la Recherche MédicaleIllkirch, France; Université de StrasbourgIllkirch, France; PHENOMIN, Institut Clinique de la Souris, Groupement d'Intérêt Économique-Centre Européen de Recherche en Biologie et en Médecine, CNRS, INSERMIllkirch-Graffenstaden, France.

Abstract

Down syndrome (DS) is one of the leading causes of intellectual disability, and patients with DS face various health issues, including learning and memory deficits, congenital heart disease, Alzheimer's disease (AD), leukemia, and cancer, leading to huge medical and social costs. Remarkable advances on DS research have been made in improving cognitive function in mouse models for future therapeutic approaches in patients. Among the different approaches, DYRK1A inhibitors have emerged as promising therapeutics to reduce DS cognitive deficits. DYRK1A is a dual-specificity kinase that is overexpressed in DS and plays a key role in neurogenesis, outgrowth of axons and dendrites, neuronal trafficking and aging. Its pivotal role in the DS phenotype makes it a prime target for the development of therapeutics. Recently, disruption of DYRK1A has been found in Autosomal Dominant Mental Retardation 7 (MRD7), resulting in severe mental deficiency. Recent advances in the development of kinase inhibitors are expected, in the near future, to remove DS from the list of incurable diseases, providing certain conditions such as drug dosage and correct timing for the optimum long-term treatment. In addition the exact molecular and cellular mechanisms that are targeted by the inhibition of DYRK1A are still to be discovered.

KEYWORDS:

DYRK1A and kinase inhibitors; clinical trial; cognition; learning and memory; mouse model; neurodevelopmental disorder; trisomy 21

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