NDLI: Tiagabine is neuroprotective in the N171-82Q and R6/2 mouse models of Huntington's disease

Content Provider	PubMed Central
Author	Masuda, Naoki Peng, Qi Li, Qing Jiang, Mali Liang, Yideng Wang, Xiaofang Zhao, Ming Wang, Wenfei Ross, Christopher A. Duan, Wenzhen
Abstract	Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by chorea, incoordination, and shortened life-span, and by huntingtin inclusions and neurodegeneration. We previously screened the 1040 FDA-approved compounds from the NINDS compound library and found that a compound, nipecotic-acid, significantly reduced mutant huntingtin aggregations and blocked cell toxicity in an inducible cell model of HD. Because nipecotic-acid does not cross the blood-brain barrier (BBB), we studied its analogue, tiagabine, which is able to cross the BBB, in both N171-82Q and R6/2 transgenic mouse models of HD. Tiagabine was administered intraperitoneally at 2 and 5 mg/kg daily in HD mice. We found that tiagabine extended survival, improved motor performance, and attenuated brain atrophy and neurodegeneration in N171-82Q HD mice. These beneficial effects were further confirmed in R6/2 HD mice. The levels of tiagabine at effective doses in mouse serum are comparable to the levels in human patients treated with tiagabine. These results suggest that tiagabine may have beneficial effects in the treatment of HD. Because tiagabine is an FDA-approved drug, it may be a promising candidate for future clinical trials for the treatment of HD.
Related Links	http://dx.doi.org/10.1016/j.nbd.2008.01.014
Ending Page	302
Page Count	10
Starting Page	293
File Format	PDF
ISSN	09699961
e-ISSN	1095953X
Journal	Neurobiology of disease
Issue Number	3
Volume Number	30
Language	English
Publisher Date	2008-06-01
Access Restriction	Open
Subject Keyword	Neurology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neurology

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