Unraveling a role for dopamine in Huntington's disease: the dual role of reactive oxygen species and D2 receptor stimulation.

ABSTRACT: Huntington's disease (HD), an inherited neurodegenerative disorder, results from an abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation leads to protein aggregation and neurotoxicity. Despite its widespread expression in the brain and body, mutated huntingtin causes selective degeneration of striatal projection neurons. In the present study, we investigate the role of dopamine (DA) in this preferential vulnerability. Using primary cultures of striatal neurons transiently expressing GFP-tagged-exon 1 of mutated huntingtin, we show that low doses of DA (100 microM) act synergistically with mutated huntingtin to activate the proapoptotic transcription factor c-Jun. Surprisingly, DA also increases aggregate formation of mutated huntingtin in all c

SUBMITTER: Charvin D 

PROVIDER: S-EPMC1189314 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature