$125,000 awarded to Dr. Maria Vera Ugalde, in collaboration with Dr. Heather D. Durham, McGill University
In ALS and many other neurodegenerative diseases, one of the defining characteristics is that proteins can become misfolded and clump together, potentially damaging nerve cells. When a healthy body responds to this type of stress, protective mechanisms increase the production of heat shock proteins (HSPs) that work like guardians inside cells helping to refold proteins so they can work again, or, if that doesn’t work, ensuring that they are destroyed.
It’s suggested in ALS that HSPs are unable to keep up with misbehaving proteins and therefore can no longer protect against trouble at the cellular level. As a treatment strategy, researchers have previously identified drugs that aim to boost the production of HSPs, however, so far, their effectiveness has been limited.
Dr. Vera Ugalde hypothesized that the expression of ALS-linked proteins within cells may interfere with the regulation of HSPs which ultimately could compromise the efficiency of HSP-boosting therapies. With this grant, Dr. Vera Ugalde will use cutting-edge single-molecule tools to study the impact of three ALS-associated genes (FUS, TARDBP, and SOD1) on the life cycle of HSPs in cell cultures, ALS mouse models and donated human tissue samples. The team will also analyze how the presence of ALS-linked proteins impact the activity of known HSP-boosting drugs and related disease mechanisms.
The results from this study will provide researchers with a more comprehensive understanding of the HSP life cycle in an ALS context, which may shed a light on why previous HSP-boosting drugs did not meet expectations and provide a framework for optimizing these types of treatments in the future.