Journal
JOURNAL OF NEUROSCIENCE
Volume 29, Issue 16, Pages 5153-5162Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0783-09.2009
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [17025044]
- Ministry of Health, Welfare, and Labor (Japan)
- [18031044]
- Grants-in-Aid for Scientific Research [17025044] Funding Source: KAKEN
Ask authors/readers for more resources
A pathological hallmark of the Huntington's disease (HD) is intracellular inclusions containing a huntingtin (Htt) protein with an elongated polyglutamine tract. Aggregation of mutant Htt causes abnormal protein-protein interactions, and the functional dysregulation of aggregate-interacting proteins (AIPs) has been proposed as a pathomechanism of HD. Despite this, a molecular mechanism remains unknown how Htt aggregates sequester AIPs. We note an RNA-binding protein, TIA-1, as a model of AIPs containing a Q/N-rich sequence and suggest that in vitro and in vivo Htt fibrillar aggregates function as a structural template for inducing insoluble fibrillation of TIA-1. It is also plausible that such a cross-seeding activity of Htt aggregates represses the physiological function of TIA-1. We thus propose that Htt aggregates act as an intracellular hub for the cross-seeded fibrillation of Q/N-rich AIPs and that a cross-seeding reaction is a molecular origin to cause diverse pathologies in a polyglutamine disease.
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