Yash Patel
McMaster University, Canada
Posters & Accepted Abstracts: J Neurol Neurophysiol
Huntington�s disease (HD) is characterized by a variety of aberrations in basic cellular processes, including epigenetic dysregulation � all attributed to the downstream effects of mutant huntingtin. The phosphorylation of two serine residues within the first 17 amino acids in huntingtin is critical in modulating the toxicity of mutant huntingtin. Increase in N17 phosphorlyation has been shown to ameloriate HD pathology, and presents a novel pharmacetical target. Epigenetic compound inhibitors were screened for a change in level of N17 phosphorlyation, and restoration of normal epigenetic regulation. An epigenetics compound screen on two cellular models of HD shows a drastic effect histone deacetylase inhibitors (HDAC) have on the level of N17 phosphorylation. Furthermore, the p53-active TruHD hTERT cell line is affected by a variety of different epigenetic compound classes such as, PARP, Aurora kinase inhibitors etc., in addition to the HDAC inhibitors found only to be effective in the p53-inactive ST Hdh Q111/Q111 cell line. TruHD hTERT cell line seems to present alternative pathways mediated through active p53 to elicit different epigenetic regulation; while ST Hdh Q111/Q111 with their inactive p53 do not show novel targets. This demonstrates the importance of having active p53 to model the true cellular physiology in Huntington�s disease. Most importantly, high content screening for therapeutic intervention should screen through TruHD hTERTs, rather than the commonly used stritals ST Hdh Q111/Q111.
Email: yp_130@me.com
