Exp Neurobiol.  2013 Dec;22(4):244-248. 10.5607/en.2013.22.4.244.

New Perspectives of Dyrk1A Role in Neurogenesis and Neuropathologic Features of Down Syndrome

• Park J
• Chung KC

• KMID: 2284627
• DOI: http://doi.org/10.5607/en.2013.22.4.244

Abstract

Down syndrome (DS) is one of the most common genetic disorders accompanying with mental retardation, cognitive impairment, and deficits in learning and memory. The brains with DS also display many neuropathological features including alteration in neurogenesis and synaptogenesis and early onset of Alzheimer's disease (AD)-like symptoms. Triplication of all or a part of human chromosome 21, especially the 21q22.1~21q22.3 region called 'Down syndrome critical region (DSCR)', has been considered as the main cause of DS. One gene product of DSCR, dual-specificity tyrosine-phosphorylation-regulated kinase 1A (Dyrk1A), has been highlighted as a key contributor to the neural consequences of DS. This minireview summarizes accumulating recent reports about Dyrk1A involvement in the neuritogenesis, synaptogenesis, and AD-like neurofibrillary tangle formation, which is mainly focusing on Dyrk1A-mediated regulation of cytoskeletal proteins, such as tubulin, actin, and microtubule-associated protein tau. Understanding the molecular mechanisms of these phenomena may provide us a rational for new preventive and therapeutic treatment of DS.

Keyword

down syndrome; Dyrk1A; neuritogenesis; synaptogenesis; cytoskeletal proteins

MeSH Terms

Actins
Alzheimer Disease
Brain
Chromosomes, Human
Cytoskeletal Proteins
Down Syndrome*
Humans
Intellectual Disability
Learning
Memory
Neurofibrillary Tangles
Neurogenesis*
Phosphotransferases
Tubulin
Actins
Cytoskeletal Proteins
Phosphotransferases
Tubulin