Objective/Rationale:
microRNAs are newly recognized, small regulatory molecules, playing important roles in normal functions and disease. However, their roles in Parkinson’s disease are still largely unknown. In this study, we will first identify microRNAs potentially involved in the genesis of PD in the brain. We will then identify microRNAs that have changed significantly in the spinal fluid of PD patients.
Project Description:
Working with samples provided by the Arizona Parkinson's Disease Consortium, we will first prepare total RNA samples from two brain regions, putamen and cortex, related to the PD and from the spinal fluid, cerebrospinal fluid (CSF) of PD patients and normal donors. We will then perform microRNA profiling to identify all microRNAs present in the two brain regions and CSF. Next, we will compare the microRNAs present in PD patients with the ones in normal human brains and CSF to identify microRNAs whose levels are significantly different in PD patients. Furthermore, we will use quantitative technologies to confirm the results and perform functional analysis to reveal potential mechanisms relating to how these microRNAs may be involved in normal functions of the brain and in the genesis of PD.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The microRNAs that are significantly different in the brains of PD patients compared to normal human brains may be involved in the genesis and/or progression of PD, and therefore, may ultimately serve as novel therapeutic targets for the treatment of PD. The microRNAs that are significantly different in the CSF of PD patients compared to normal human CSF may serve as diagnostic markers for the onset and/or progression of PD.
Anticipated Outcome:
This research will identify 1) all microRNAs present in the two brain regions, putamen and cortex, and the CSF of normal controls and PD patients; 2) lists of microRNAs that are significantly different in the brains and CSF of PD patients compared to normal human samples. These findings will yield a substantial body of novel knowledge on human neurobiology and molecular bases for PD and open numerous new directions for future research on PD and related diseases.
Final Outcome
The goal of this study was to identify microRNAs (miRNAs) involved in Parkinson’s disease and identify those in cerebrospinal fluid (CSF) that are significantly different from the miRNAs in the CSF of healthy controls as well as people with other illnesses. We successfully identified a series of miRNAs that differed among the various conditions and also identified miRNAs whose expression levels correlate to disease progression. Ultimately, we found novel potential therapeutic targets and potential diagnostic biomarkers. Further validation of these miRNAs will lead to clinical trials for early detection and efficient treatment of PD.
Presentations & Publications
The goal of this study was to identify microRNAs (miRNAs) involved in Parkinson’s disease and identify those in cerebrospinal fluid (CSF) that are significantly different from the miRNAs in the CSF of healthy controls as well as people with other illnesses. We successfully identified a series of miRNAs that differed among the various conditions and also identified miRNAs whose expression levels correlate to disease progression. Ultimately, we found novel potential therapeutic targets and potential diagnostic biomarkers. Further validation of these miRNAs will lead to clinical trials for early detection and efficient treatment of PD.