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2014 Grants - Sephton
FUS in Synaptic Function and Frontotemporal Lobar Degeneration
Chantelle F. Sephton, Ph.D.
Quebec City, Quebec, Canada
2014 New Investigator Research Grant
Synapses are specialized structures through which nerve cells communicate with other nerve cells. Functional synapses are essential for many of the unique capabilities of the brain, including learning and memory. In both Alzheimer’s disease and another type of dementia known as frontotemporal lobar degeneration (FTLD), synaptic function becomes impaired in the early stages of the disease process.
FUS (an abbreviation for ‘fused in sarcoma’) is the name of a protein implicated in the development of FTLD. The FUS protein forms clumps in the brains of people with FTLD, similar to the amyloid plaques formed from the clumping of the beta-amyloid protein in the brains of people with Alzheimer’s disease. Some cases of FTLD involve alterations in the FUS gene, but how these changes may affect synaptic function in nerve cells is not well understood.
Chantelle F. Sephton, Ph.D., and colleagues have been studying the role of the FUS protein in FTLD. Using mice engineered to have an abnormal version of the FUS protein associated with FTLD, the researchers showed that synapses in the brain become impaired and are then lost as the disease progresses. They have proposed further studies to understand how alterations in FUS may lead to loss of synaptic function and nerve cell degeneration in FTLD. Dr. Sephton’s team will use their genetically engineered mice and nerve cells growing in laboratory dishes to study how different versions of the FUS protein affect synaptic function. These studies will help advance our understanding of the molecular mechanisms involved in the development and progression of FTLD, and may suggest new ways to prevent the loss of synaptic function in neurodegenerative brain diseases.