Huntingtin (D7F7) Rabbit Monoclonal Antibody (BSA and Azide Free)#31873,Cell Signaling Technology (CST),31873

Huntington's Disease (HD) is a fatal neurodegenerative disorder characterized by psychiatric, cognitive, and motor dysfunction. HD neuropathology involves the selective degeneration of specific neuronal subpopulations, including GABA-ergic neurons of the striatum and those within the cerebral cortex (1,2). The genetic analysis of HD has been the flagship study of inherited neurological diseases, from initial chromosomal localization to identification of the gene.Huntingtin is a large (340-350 kDa) cytosolic protein that may be involved in a number of cellular functions such as transcription, gastrulation, neurogenesis, neurotransmission, axonal transport, neural positioning, and apoptosis (2,3). TheHDgene from unaffected individuals contains between 6 and 34 CAG trinucleotide repeats, with expansion beyond this range causing the onset of disease symptoms. A strong inverse correlation exists between the age of onset in patients and the number of huntingtin gene CAG repeats encoding a stretch of polyglutamine peptides (1,2). The huntingtin protein undergoes numerous post-translational modifications, including phosphorylation, ubiquitination, sumoylation, palmitoylation, and cleavage (2). Phosphorylation of Ser421 by Akt can partially counteract the toxicity that results from the expanded polyglutamine tract. Varying Akt expression in the brain correlates with regional differences in huntingtin protein phosphorylation; this pattern inversely correlates with the regions that are most affected by degeneration in diseased brain (2). A key step in the disease is the proteolytic cleavage of huntingtin protein into amino-terminal fragments that contain expanded glutamine repeats and translocate into the nucleus. Caspase-mediated cleavage of huntingtin at Asp513 is associated with increased polyglutamine aggregate formation and toxicity. Phosphorylation of Ser434 by CDK5 protects against cleavage (2,3).Gusella, J.F. and Macdonald, M.E. (2006)Trends Biochem. Sci.31, 533-540.Borrell-Pagès, M. et al. (2006)Cell Mol. Life Sci.63, 2642-2660.Luo, S. et al. (2005)J. Cell Biol.169, 647-656.Alternate NamesHD; HD protein; HTT; Huntingtin; Huntingtin, myristoylated N-terminal fragment; Huntington disease protein; IT15; LOMARS

HD; HD protein; HTT; Huntingtin; Huntingtin, myristoylated N-terminal fragment; Huntington disease protein; IT15; LOMARS