Funded Studies
Objective/Rationale:
We propose studies to address the overall hypothesis that small ribonucleic acids (RNAs) – molecules that code and regulate genes –contribute to the type of tau protein expressed in the cell. Tau is an important player in neurodegenerative diseases and has been implicated in Parkinson’s disease (PD). This protein exists in two different forms, one of which is associated with neuronal dysfunction and disease.
Project Description:
We will use standard procedures with materials harvested from human brain, and other studies in cultured cells to address our fundamental hypothesis.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Our data may have relevance for diagnostic tests and therapies for PD. If we find in this work that small RNAs in the cell impact the type of tau expressed, which in turn impacts cell viability, tests could be developed to determine if an individual has the gene sequence that may increase the risk for neurodegenerative disease. Therapies that mitigate this risk would also be a focus of development.
Anticipated Outcome:
We expect to learn that tau can be regulated by small RNAs in the cell, and that this impacts the type of tau that is expressed in brain cells. Because the type of tau present in cells can impact the health of that cell, our findings will be relevant for PD and other neurodegenerative diseases.
Progress Report
Small ribonucleic acids (RNAs) are molecules that regulate genes and their products, proteins. In this study, we hypothesized that small RNAs control the production of tau -- a protein that clumps in the brains of people with Parkinson's disease (PD) -- and whether it causes neurodegeneration. We identified miR-181, a small RNA that regulates tau. This finding may explain previously discovered connection between miR-181 and neurofibrillary tangles -- toxic clumps of tau -- in the human brain. Furthermore, similar RNAs are currently being studied as disease targets that can be controlled -- turned on or off -- with drugs. Our results may help guide these studies. Overall, our findings support future studies of the regulation and role of miR-181 in neurodegenerative disease and of the factors, such as aging and environment, that influence miR-181 levels in the brain.
September 2014