DYRK1A

Class

DYRK1A inhibitor

DYRK1A (dual-specificity tyrosine-phosphorylation-regulated kinase 1A) is an enzyme that adds phosphate groups to other proteins, thereby switching their activity on or off. It is highly expressed in the brain and plays a role in neuronal development, synaptic function, and the regulation of proteins implicated in neurodegeneration, including tau and amyloid precursor protein. The gene encoding DYRK1A resides on chromosome 21; individuals with an extra copy of this chromosome (trisomy 21, the cause of Down syndrome) have elevated DYRK1A activity, which has been linked to altered brain development and to the early, aggressive amyloid and tau pathology characteristic of Alzheimer's disease in this population. Because of this dosage-sensitive biology, reducing excess DYRK1A kinase activity with a small-molecule inhibitor is a rational strategy for addressing cognitive and neurodegenerative features associated with chromosome 21 trisomy. More broadly, DYRK1A modulation is of interest wherever aberrant phosphorylation of tau or cell-cycle regulators contributes to neuronal dysfunction, extending potential relevance to other neurodegenerative and neurodevelopmental conditions beyond Down syndrome specifically.