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Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview

Perha Pharmaceuticals, Perharidy Peninsula, 29680 Roscoff, France
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Author to whom correspondence should be addressed.
Academic Editor: Ana Martínez
Int. J. Mol. Sci. 2021, 22(11), 6047; https://doi.org/10.3390/ijms22116047
Received: 30 April 2021 / Revised: 26 May 2021 / Accepted: 28 May 2021 / Published: 3 June 2021
(This article belongs to the Special Issue Protein Kinases and Their Inhibitors in CNS Diseases)
Dual-specificity tyrosine phosphorylation-regulated kinases (DYRK1A, 1B, 2-4) and cdc2-like kinases (CLK1-4) belong to the CMGC group of serine/threonine kinases. These protein kinases are involved in multiple cellular functions, including intracellular signaling, mRNA splicing, chromatin transcription, DNA damage repair, cell survival, cell cycle control, differentiation, homocysteine/methionine/folate regulation, body temperature regulation, endocytosis, neuronal development, synaptic plasticity, etc. Abnormal expression and/or activity of some of these kinases, DYRK1A in particular, is seen in many human nervous system diseases, such as cognitive deficits associated with Down syndrome, Alzheimer’s disease and related diseases, tauopathies, dementia, Pick’s disease, Parkinson’s disease and other neurodegenerative diseases, Phelan-McDermid syndrome, autism, and CDKL5 deficiency disorder. DYRKs and CLKs are also involved in diabetes, abnormal folate/methionine metabolism, osteoarthritis, several solid cancers (glioblastoma, breast, and pancreatic cancers) and leukemias (acute lymphoblastic leukemia, acute megakaryoblastic leukemia), viral infections (influenza, HIV-1, HCMV, HCV, CMV, HPV), as well as infections caused by unicellular parasites (Leishmania, Trypanosoma, Plasmodium). This variety of pathological implications calls for (1) a better understanding of the regulations and substrates of DYRKs and CLKs and (2) the development of potent and selective inhibitors of these kinases and their evaluation as therapeutic drugs. This article briefly reviews the current knowledge about DYRK/CLK kinases and their implications in human disease. View Full-Text
Keywords: DYRKs; CLKs; kinase; kinase inhibitor; Alzheimer’s disease; Down syndrome; type 1 diabetes; type 2 diabetes; acute lymphoblastic leukemia; viral infections DYRKs; CLKs; kinase; kinase inhibitor; Alzheimer’s disease; Down syndrome; type 1 diabetes; type 2 diabetes; acute lymphoblastic leukemia; viral infections
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MDPI and ACS Style

Lindberg, M.F.; Meijer, L. Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview. Int. J. Mol. Sci. 2021, 22, 6047. https://doi.org/10.3390/ijms22116047

AMA Style

Lindberg MF, Meijer L. Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview. International Journal of Molecular Sciences. 2021; 22(11):6047. https://doi.org/10.3390/ijms22116047

Chicago/Turabian Style

Lindberg, Mattias F., and Laurent Meijer. 2021. "Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview" International Journal of Molecular Sciences 22, no. 11: 6047. https://doi.org/10.3390/ijms22116047

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