Targeting Transcriptional Dysregulation in Huntington’s Disease: Description of Therapeutic Approaches

摘要: Huntington’s Disease (HD) is a dominantly inherited neurodegenerative disease affecting cognitive, emotional and motor systems. While alterations in the huntingtin gene (HTT) have been identified as causative for nearly two decades, an effective treatment has yet to be developed. Prior studies shown that mutant (mHTT), via its polyglutamineexpanded repeats, can affect cellular function many ways, such alteration of transcription, one best-characterized pathobiological events leading HD. Microarray mouse models HD postmortem brain samples from patients report decrease transcriptional levels hundreds genes, most them selectively expressed striatum, affected region mHTT inhibit interactions several transcription factors repress genes necessary neuronal survival, Brain Derived Neurotrophin (BDNF) or co-activator Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-alpha).