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Transient osmotic stress facilitates mutant huntingtin aggregation
Wanjoo Chun1, Mathieu Lesort, Matthew Lee
1Department of Psychiatry and Behavioral Neurobiology, 1720 7th Avenue South, SC1061, University of Alabama at Birmingham, Birmingham, AL 35294-0017, USA.
Neuroreport
|December 25, 2002
Summary
Hyperosmotic stress increases mutant huntingtin aggregation in neuronal cells. This aggregation, potentially seeded by microaggregates, is partially reduced by activating heat shock responses.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Huntington's disease is a neurodegenerative disorder characterized by the aggregation of mutant huntingtin protein.
- Cellular stress pathways can influence the formation and progression of protein aggregates.
Purpose of the Study:
- To investigate the effect of hyperosmotic stress on mutant huntingtin (N63-82Q) aggregation in SH-SY5Y cells.
- To explore the role of microaggregate formation and heat shock response in modulating this aggregation.
Main Methods:
- Utilized human neuroblastoma SH-SY5Y cell lines expressing N63-82Q.
- Applied transient hyperosmotic treatment and subsequent return to iso-osmotic conditions.
- Administered geldanamycin to activate heat shock response.
Main Results:
- Hyperosmotic stress transiently increased N63-82Q concentration and significantly raised the number of cells with aggregates.
- Aggregate formation continued to increase between 12 and 24 hours post-treatment, reaching ~55% of cells.
- Geldanamycin treatment significantly attenuated the hyperosmotic-induced increase in aggregate formation.
Conclusions:
- Hyperosmotic stress promotes mutant huntingtin aggregation, possibly via seeding mechanisms.
- The heat shock response can mitigate stress-induced huntingtin aggregation.