Objective/Rationale:
Brain infiltration of T cells has been identified in patients with Parkinson's disease and implicated in neurodegeneration in pre-clinical models. We hypothesize that peripheral T cells migrate into the brain through a tightly regulated mechanism. In another study funded by the MJFF, we identified several candidates in a pre-clinical model of the disease. To compare our experimental data with the real pathology, we wish to conduct a postmortem analysis using human tissue specimens.
Project Description:
Our study has been designed to answer the following critical questions: Are candidates modulated broadly or in lesioned brain areas only in Parkinson's disease? Are candidates modulated in various neurological disorders or in Parkinson's disease only? To answer those questions, brain tissue samples from patients with Parkinson's disease, Alzheimer's disease, multiple sclerosis and individuals with no history of neurological disorders will be collected. Gene expression level of candidates will be assessed and compared on the one hand, between affected and non-affected brain regions in Parkinson's disease and, on the other hand, between patients with Parkinson's disease and other neurological conditions and control subjects. A total of 33 individuals per group of patients will be analyzed. Eventually, immunohistochemical detection of most promising candidates will be performed on additional human tissue sections.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Glial and peripheral immune cells are increasingly recognized as important factors in progressive neuronal loss in neurodegenerative disorders such as Parkinson's disease. In line with this, preventing peripheral immune cells from entering the injured brain may provide protective benefits by decreasing inflammation. Our proposed investigations have the potential to unravel such mechanisms and thus to fuel the field of drug development for Parkinson's disease patients.
Anticipated Outcome:
Data obtained from this project should add significant value to our selection process of candidates for future target validation studies.