Journal
SCIENCE
Volume 293, Issue 5529, Pages 493-498Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1059581
Keywords
-
Categories
Funding
- Telethon [E.0840] Funding Source: Medline
Ask authors/readers for more resources
Huntingtin is a 350-kilodalton protein of unknown function that is mutated in Huntington's disease (HD), a neurodegenerative disorder. The mutant protein is presumed to acquire a toxic gain of function that is detrimental to striatal neurons in the brain. However, Loss of a beneficial activity of wild-type huntingtin may also cause the death of striatal neurons. Here we demonstrate that wild-type huntingtin up-regulates transcription of brain-derived neurotrophic factor (BDNF), a pro-survival factor produced by cortical neurons that is necessary for survival of striatal neurons in the brain. We show that this beneficial activity of huntingtin is Lost when the protein becomes mutated, resulting in decreased production of cortical BDNF. This Leads to insufficient neurotrophic support for striatal neurons, which then die. Restoring wild-type huntingtin activity and increasing BDNF production may be therapeutic approaches for treating HD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available