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2016 Grants - Salta
Functional Validation of miR-132 Loss in Alzheimer’s Disease and Therapeutic Targeting
Evgenia Salta, Ph.D.
Flanders Interuniversity Institute for Biotechnology (VIB)
2016 Alzheimer’s Association Research Fellowship (AARF)
Can a molecule that regulates gene activity help prevent brain changes associated with Alzheimer’s disease?
Small molecules called microRNAs (miRNAs) affect what genes are turned on/off and therefore can impact many important biological processes. Research suggests that alterations in certain types of miRNAs may promote Alzheimer’s disease, but the exact mechanisms remain unclear. In previous studies, Evgenia Salta, Ph.D., and others have shown that levels of a miRNA called miR-132 are abnormally low in brain tissue from people who had Alzheimer’s disease. Dr. Salta’s team has also found that blocking production of miR-32 in Alzheimer’s-like mice leads to build-up of abnormal tau protein in the brain. Accumulation of tau “tangles” in the brain is a hallmark of Alzheimer’s disease. Taken together, these findings suggest that miR-132 may help protect the health of brain cells, and that its loss may contribute to brain changes associated with Alzheimer’s.
For their current studies, Dr. Salta and colleagues plan to clarify the links between miR-132 and Alzheimer’s disease. The researchers will use several different mouse models of Alzheimer’s disease to determine how miR-32 inhibition affects the build-up of abnormal tau and beta-amyloid in the brain. Beta-amyloid is a protein fragment that forms plaques, another hallmark of Alzheimer’s disease. They also plan to identify genes and proteins that are regulated by miR-32 and determine how they may be involved in Alzheimer’s disease. Lastly, Dr. Salta and colleagues will test whether treating the Alzheimer’s-like mice with a miR-32 replacement therapy can prevent disease-related brain changes and improve memory function.
The results of these studies could shed new light on how changes in miRNAs may contribute to the molecular mechanisms of Alzheimer’s disease. Importantly this effort could identify miR-132, or drugs that mimic its effect, as a novel therapy for Alzheimer’s disease.