DYRK1A (Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A), a Master Regulatory Protein Involved in Down Syndrome Clinical Neurological Abnormalities and Associated Mental Retardation and a Promising Potential Drug Target for Therapeutics and Treatments

Abstract

Over-expression of chromosome 21 genes, particularly in Down Syndrome Critical Region (DSCR), is the main cause of Down syndrome (DS) neuropathological features including mental retardation, cognitive impairments and early onset of Alzheimer’s disease. One of DSCR genes, that we studied herein, DYRK1A (Dual-Specificity Tyrosine-Phosphorylation-Regulated Kinase 1A), is a master regulatory protein involved in DS neuropathological features and associated mental retardation. Interestingly, normalization of DYRK1A over-expression by DYRK1A inhibitor, epigalloctechin-3-gallate (EGCG), rescues brain defects, restores cognitive impairments in DS trisomic and DYRK1A transgenic mouse models and in DS patients. These results indicates DYRK1A inhibitor epigalloctechin-3-gallate (EGCG) as an effective treatment and DYRK1A as a key regulatory protein involved in DS clinical neuropathological features suggesting DYRK1A as a valuable potential drug target for therapeutics and Treatments of DS and mental retardation opening new directions for developing new medical preventive and therapeutic treatments.