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2016 Grants - Karunakaran
Molecular Mechanisms of the Alzheimer’s Risk Gene UNC5c in Neuronal Death
Devi Krishna Priya Karunakaran, Ph.D.
2016 Alzheimer’s Association Research Fellowship (AARF)
Does a variation in a gene related to brain development increase the risk of Alzheimer’s disease?
Several genetic variations have been identified that can increase a person’s risk of developing Alzheimer’s disease. Recent studies have found that a specific variation in gene called Unc-5 netrin receptor C (UNC5c) may be associated with Alzheimer’s risk, but the underlying mechanisms are not yet known. Normally, the UNC5c gene helps control brain development. However, a variation in the UNC5c gene is thought to alter its function and make nerve cells more vulnerable to the harmful effects of beta-amyloid. Beta-amyloid is a protein fragment that can form “plaques” in the brain – a hallmark of Alzheimer’s disease.
Devi Krishna Priya Karunakaran, Ph.D., and colleagues have proposed a series of studies to determine how the UNC5c genetic variation may relate to nerve cell damage and death in Alzheimer’s disease. They will genetically modify nerve cells growing in laboratory dishes to carry the UNC5c variation and expose them to beta-amyloid. They will determine if UNC5c promotes changes in specific molecules associated with nerve cell death. The researchers will also study Alzheimer’s-like mice engineered to have the UNC5c genetic risk factor to determine how this impacts nerve cell loss and memory function over time.
These studies could help scientists better understand how certain genetic variations increase the risk of Alzheimer’s disease. Ultimately this work could help guide the development of new drugs to prevent or reverse nerve cell loss in Alzheimer’s and other neurodegenerative diseases.