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2017 Grants - Fioriti
Role of SUMOylation in the Aggregation and Toxicity of Tau
Luana Fioriti, Ph.D.
Mario Negri Institute for Pharmaceutical Research
2017 Alzheimer’s Association Research Grant (AARG)
How does a chemical modification called SUMOylation affect the formation of tau tangles in the brain?
Tau is a protein that normally functions to support nerve cell structure and help transport nutrients within the cell. In Alzheimer’s disease, tau can accumulate and clump into tau tangles in the brain, one of the hallmarks of the disease. Proteins such as tau can be chemically modified in several different ways that make them more or less likely to clump together — a process known as aggregation. Recent studies suggest that a chemical modification that involves SUMOs (small ubiquitin-like modifiers) may make proteins less likely to clump. More research is needed to determine if “SUMOylation” plays a role in regulating the tendency for tau to form tangles in the brain and how this may impact Alzheimer’s disease.
Luana Fioriti, Ph.D., and colleagues will use nerve cells grown in laboratory dishes to determine if SUMOylation of tau can reduce its ability to form toxic clumps. Their initial studies found that increased levels of a specific variant called Sumo2 was particularly effective at reducing tau aggregation. For their current studies, they will treat nerve cells with Sumo2 and measure its ability to prevent or reduce the formation of tau tangles. They will also determine if Sumo2 can prevent the spreading of abnormal tau between nerve cells — a mechanism thought to underlie the progressive brain changes associated with Alzheimer’s disease. The researchers also hope to identify the biological pathways that regulate the SUMOylation of tau so that they can be targeted for the development of future therapies.
The results of these studies will provide new information on the molecular mechanisms involved in the formation of tau tangles in the brain. This work could also lay the foundation for future experiments to determine if therapies that promote SUMOlyation could help prevent or treat Alzheimer’s disease.