Large-scale transcriptomic analysis reveals that pridopidine reverses aberrant gene expression and activates neuroprotective pathways in the YAC128 HD mouse.

ABSTRACT:

Background

Huntington Disease (HD) is an incurable autosomal dominant neurodegenerative disorder driven by an expansion repeat giving rise to the mutant huntingtin protein (mHtt), which is known to disrupt a multitude of transcriptional pathways. Pridopidine, a small molecule in development for treatment of HD, has been shown to improve motor symptoms in HD patients. In HD animal models, pridopidine exerts neuroprotective effects and improves behavioral and motor functions. Pridopidine binds primarily to the sigma-1 receptor, (IC50 ~ 100 nM), which mediates its neuroprotective properties, such as rescue of spine density and aberrant calcium signaling in HD neuronal cultures. Pridopidine enhances brain-derived neurotrophic factor (BDNF) secretion, which is blocked by putative sigma-

SUBMITTER: Kusko R 

PROVIDER: S-EPMC5963017 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature