tailieunhanh - Báo cáo khoa học: The role of DYRK1A in neurodegenerative diseases

Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene, which is located on chromosome and is overexpressed in Down syndrome (DS), may play a signifi-cant role in developmental brain defects and in early onset neurodegenera-tion, neuronal loss and dementia in DS. | ịFEBS Journal MINIREVIEW The role of DYRK1A in neurodegenerative diseases Jerzy Wegiel1 Cheng-Xin Gong2 and Yu-Wen Hwang3 1 Department of DevelopmentalNeurobiology New York State Institute for Basic Research in DevelopmentalDisabilities Staten Island NY USA 2 Department of Neurochemistry New York State Institute for Basic Research in DevelopmentalDisabilities Staten Island NY USA 3 Department of Molecular Biology New York State Institute for Basic Research in DevelopmentalDisabilities Staten Island NY USA Keywords alternative splicing factor Alzheimer s disease amyloid-b peptide Down syndrome DYRK1A neurodegeneration tau phosphorylation a-synuclein Correspondence J. Wegiel New York State Institute for Basic Research in Developmental Disabilities 1050 Forest HillRoad Staten Island NY 10314 USA Fax 718 494 4856 Tel 718 494 5231 E-mail Received 16 July 2010 revised 5 October 2010 accepted 5 November 2010 doi Recent studies indicate that the dual-specificity tyrosine phosphorylation-regulated kinase 1A DYRK1A gene which is located on chromosome and is overexpressed in Down syndrome DS may play a significant role in developmental brain defects and in early onset neurodegeneration neuronal loss and dementia in DS. The identification of hundreds of genes deregulated by DYRK1A overexpression and numerous cytosolic cytoskeletal and nuclear proteins including transcription factors phosphorylated by DYRK1A indicates that DYRK1A overexpression is central for the deregulation of multiple pathways in the developing and aging DS brain with structural and functional alterations including mental retardation and dementia. DYRK1A overexpression in DS brains may contribute to early onset neurofibrillary degeneration directly through hyperphosphorylation of tau and indirectly through phosphorylation of alternative splicing factor leading to an imbalance between 3R-tau and 4R-tau. The several-fold increases in the .