| Literature DB >> 18403212 |
Wenzhen Duan1, Qi Peng2, Naoki Masuda2, Eric Ford3, Erik Tryggestad3, Bruce Ladenheim4, Ming Zhao5, Jean Lud Cadet4, John Wong3, Christopher A Ross6.
Abstract
Huntington's disease (HD) is an inherited progressive neurodegenerative disorder resulting from CAG repeat expansion in the gene that encodes for the protein huntingtin. To identify neuroprotective compound (s) that can slow down disease progression and can be administered long term with few side effects in Huntington's disease, we investigated the effect of sertraline, a selective serotonin reuptake inhibitor (SSRI) which has been shown to upregulate BDNF levels in rodent brains. We report here that in HD mice sertraline increased BDNF levels, preserved chaperone protein HSP70 and Bcl-2 levels in brains, attenuated the progression of brain atrophy and behavioral abnormalities and thereby increased survival. Sertraline also enhanced neurogenesis, which appeared to be responsible for mediating the beneficial effects of sertraline in HD mice. Additionally, the effective levels of sertraline are comparable to the safe levels achievable in humans. The findings suggest that sertraline is a potential candidate for treatment of HD patients.Entities:
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Year: 2008 PMID： 18403212 PMCID： PMC3683653 DOI： 10.1016/j.nbd.2008.01.015
Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996