Abstract
UBB+1, a mutant form of ubiquitin, is both a substrate and an inhibitor of the proteasome which accumulates in the neuropathological hallmarks of Huntington disease (HD). In vitro, expression of UBB+1 and mutant huntingtin synergistically increase aggregate formation and polyglutamine induced cell death. We generated a UBB+1 transgenic mouse line expressing UBB+1 within the neurons of the striatum. In these mice lentiviral driven expression of expanded huntingtin constructs in the striatum results in a significant increase in neuronal inclusion formation. Although UBB+1 transgenic mice show neither a decreased lifespan nor apparent neuronal loss, they appear to be more vulnerable to toxic insults like expanded polyglutamine proteins due to a modest proteasome inhibition. These findings underscore the relevance of an efficient ubiquitin-proteasome system in HD.
Original language | English |
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Pages (from-to) | 281-286 |
Journal | Molecular and Cellular Neuroscience |
Volume | 43 |
Issue number | 3 |
DOIs | |
Publication status | Published - Mar 2010 |
Keywords
- Polyglutamine disease
- Ubiquitin proteasome system
- Neurodegeneration
- Transgenic mice
- Inclusions
- Huntingtin