Understanding the Multifaceted Role of Human Down Syndrome Kinase DYRK1A

Abstract

The dual-specificity tyrosine (Y) phosphorylation-regulated kinase DYRK1A, also known as Down syndrome (DS) kinase, is a dosage-dependent signaling kinase that was originally shown to be highly expressed in DS patients as a consequence of trisomy 21. Although this was evident some time ago, it is only in recent investigations that the molecular roles of DYRK1A in a wide range of cellular processes are becoming increasingly apparent. Since initial knowledge on DYRK1A became evident through minibrain mnb, the Drosophila homolog of DYRK1A, this review will first summarize the scientific reports on minibrain and further expand on the well-established neuronal functions of mammalian and human DYRK1A. Recent investigations across the current decade have provided rather interesting and compelling evidence in establishing nonneuronal functions for DYRK1A, including its role in infection, immunity, cardiomyocyte biology, cancer, and cell cycle control. The latter part of this review will therefore focus in detail on the emerging nonneuronal functions of DYRK1A and summarize the regulatory role of DYRK1A in controlling Tau and α-synuclein. Finally, the emerging role of DYRK1A in Parkinson's disease will be outlined