{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T12:00:08Z","timestamp":1790510408830,"version":"4.1.0"},"reference-count":259,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T00:00:00Z","timestamp":1622678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["848077"],"award-info":[{"award-number":["848077"]}]},{"DOI":"10.13039\/100007353","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","award":["-"],"award-info":[{"award-number":["-"]}],"id":[{"id":"10.13039\/100007353","id-type":"DOI","asserted-by":"publisher"}]},{"name":"\u201cAgence Nationale pour la Recherche (ANR)\u201d (DYRK-DOWN)","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2019s disease and related diseases, tauopathies, dementia, Pick\u2019s disease, Parkinson\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms22116047","type":"journal-article","created":{"date-parts":[[2021,6,3]],"date-time":"2021-06-03T10:59:51Z","timestamp":1622717991000},"page":"6047","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinases (DYRKs) and cdc2-Like Kinases (CLKs) in Human Disease, an Overview"],"prefix":"10.3390","volume":"22","author":[{"given":"Mattias F.","family":"Lindberg","sequence":"first","affiliation":[{"name":"Perha Pharmaceuticals, Perharidy Peninsula, 29680 Roscoff, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-4916","authenticated-orcid":false,"given":"Laurent","family":"Meijer","sequence":"additional","affiliation":[{"name":"Perha Pharmaceuticals, Perharidy Peninsula, 29680 Roscoff, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zhang, H., Cao, X., Tang, M., Zhong, G., Si, Y., Li, H., Zhu, F., Liao, Q., Li, L., and Zhao, J. 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