Regulation of type 1 cannabinoid receptor expression in Huntington's disease.

Huntington's disease (HD) is a neurodegenerative disorder caused by inheritance of a single copy of the huntingtin gene containing an expanded CAG repeat. The type 1 cannabinoid receptor (CB1) is a G-protein coupled receptor (GPCR), whose transcription declines early in HD progression. The early incidence of CB1 reduction in HD suggests decreased transcription is a direct effect of the mutant huntingtin protein (mHtt). However, the mechanism of mHtt-dependent CB1 decline is poorly understood, as are the consequences of decreased CB1 expression on GPCR signalling. The goal of my research is to define the mechanisms by which mHtt represses transcription of CB1, and the repercussions of decreased CB1 expression on GPCR signalling. CB1 is an important target in HD because it has several neuroprotective roles. Moreover, therapies targeting CB1 are currently being investigated for other neurodegenerative disorders, such as Alzheimer's disease and Multiple Sclerosis. Therefore, this work will enhance our understanding of HD and the importance of CB1, a potential therapeutic target, therein.