Funded Studies
Study Rationale:
While most cases of Parkinson's disease (PD) have no known cause, some are caused by changes (mutations) in genes such as SNCA, which regulates the production of a protein called alpha-synuclein. Alpha-synuclein is a sticky protein that clumps in the brains of people with PD. In our recent work, we have been focusing on identifying the exact location of alpha-synuclein inside the cell. One such location is the mitochondria, powerhouses of the cell. Mitochondria attached to endoplasmic reticulum -- a network of tiny tubes inside the cell -- are known as mitochondria-associated endoplasmic reticulum membranes (MAM). MAM regulates several important cellular functions, one of which is the production and breakdown of molecules called phospholipids.
Hypothesis:
We have previously observed changes in phospholipids in pre-clinical models with Parkinson's features. We hypothesize that changes in mitochondria seen in PD can be due, at least in part, to changes in phospholipids, specifically, due to reduced levels of phospholipid phosphatidylethanolamine (PtdEtn).
Study Design:
We will evaluate the levels, production and breakdown of PtdEtn in blood samples collected at Columbia University Medical Center from people with Parkinson's disease and from healthy people.
Impact on Diagnosis/Treatment of Parkinson's Disease:
The goal of this project is to study PtdEtn as a biomarker -- objective measure of disease -- to diagnose and monitor PD progression.
Next Steps for Development:
Our findings could guide high-throughput screening of drugs that can reverse PD-associated changes in the phospholipid pathway and in the mitochondria.