Neuroprotective Effects of Phenylbutyrate in the N171-82Q Transgenic Mouse Model of Huntington's Disease

摘要: Huntington's disease (HD) is caused by an expansion of exonic CAG triplet repeats in the gene encoding huntingtin protein (Htt), however, means which neurodegeneration occurs remains obscure. There evidence that mutant Htt interacts with transcription factors leading to reduced histone acetylation. We report administration deacetylase inhibitor phenylbutyrate after onset symptoms a transgenic mouse model HD significantly extends survival and attenuates both gross brain neuronal atrophy. Administration increased acetylation decreased methylation levels as assessed immunocytochemistry Western blots. Phenylbutyrate mRNA for components ubiquitin-proteosomal pathway down-regulated caspases implicated apoptotic cell death, active caspase 3 immunoreactivity striatum. These results show phenylbutyrate, at doses are well tolerated man, exerts significant neuroprotective effects HD, therefore represents very promising therapeutic approach HD.