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2008 Grants - Nelson
Mechanism and Therapeutic Significance of an Alzheimer's Disease–Relevant MicroRNA Pathway
Peter T. Nelson, M.D., Ph.D.
University of Kentucky Research Foundation
2008 New Investigator Research Grant
Ribonucleic acids (RNA) are long-stranded molecules with numerous functions within cells, the most common of which is to serve as the "messenger" template for the creation of proteins based on their genetic sequence stored in DNA. Appropriately, such RNA are called messenger RNA (mRNA). Recently, another type of RNA, microRNA, has been discovered. MicroRNAs regulate how genes are expressed, and some have been implicated in diseases such as cancer.
The possible roles of microRNAs in Alzheimer's disease have not been studied in detail, but Peter T. Nelson, M.D., Ph.D., and colleagues have preliminary evidence suggesting that one type of microRNA (miR-107) may be involved in Alzheimer pathology. Specifically, they suspect that miR-107 may control the expression of the protein BACE1, which is involved in the production of beta-amyloid, a key suspect in Alzheimer pathology.
Dr. Nelson and colleagues plan to use model nerve cells growing in culture to study how miR-107 regulates the expression of BACE1 and the subsequent production of beta-amyloid. The researchers will also study how the drug bezafibrate affects miR-107 and BACE1 levels. Bezafibrate is a well-known drug used for reducing blood lipid levels, but preliminary evidence also suggests that it increases levels of miR-107 and decreases levels of BACE1.
These studies will probe some of the fundamental molecular mechanisms controlling the production of beta-amyloid, and they may provide information about the potential usefulness of a drug for reducing production of this damaging protein fragment. Such information could set the stage for clinical trials of new drugs to slow or halt the progression of Alzheimer's disease.