Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) (DYRK1A)

Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is a highly conserved protein kinase belonging to the CMGC family, located on chromosome 21 in the Down syndrome critical region [1, 3, 13]. It plays a pivotal role in neurodevelopment, cell cycle regulation, and various signaling pathways by phosphorylating a wide range of substrates, including transcription factors and cytoskeletal proteins [2, 4, 6]. DYRK1A is a dosage-sensitive enzyme; its overexpression is a primary driver of cognitive deficits and early-onset Alzheimer's disease in Down syndrome, while its haploinsufficiency leads to a specific syndrome characterized by microcephaly and intellectual disability [5, 18, 22]. In addition to neurodevelopmental roles, DYRK1A is implicated in cancer progression, diabetes (by regulating beta-cell proliferation), and viral infections [1, 6, 16]. Therapeutic strategies primarily focus on small-molecule inhibitors, such as harmine and epigallocatechin gallate (EGCG), which aim to normalize kinase activity in conditions of overexpression [9, 14, 23]. However, maintaining the delicate balance of its activity remains a significant clinical challenge due to its essential role in normal physiology [18, 22].

Other names

DYRK1DYRKMNBMNBHHP86MRD7Dual specificity tyrosine-phosphorylation-regulated kinase 1A

ATP-competitive inhibition of the kinase domain