Objective/Rationale:
The protein alpha-synuclein aggregates abnormally in brain tissue affected by Parkinson’s disease. The present project is a follow up on a project that generated a panel of antibodies that recognize aggregated alpha-synuclein. The present project will characterize these antibodies for their qualities in recognizing aggregates of alpha-synuclein in brain tissue and extracts of brain and will facilitate the decision on what antibodies to bring to the scientific community.
Project Description:
A panel of new pre-clinical monoclonal antibodies against aggregated alpha-synuclein will be analyzed. First methods to optimize the specificity will be conducted. Second native gel electrophoretic procedures will be optimized that allows the detection of aggregated alpha-synuclein made in the laboratory. When the procedures have been optimized, extracts from normal control and Parkinson’s brain tissue will be analyzed by electrophoresis. Third, the information for the individual antibodies will be used to guide subsequent microscopical analyses of human brain slices from normal control and Parkinson’s patients prepared under different conditions. The project should demonstrate which of the antibodies are best suited to detect aggregated alpha-synuclein species in human brain samples.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
The aim is to provide new tools that will improve diagnostic procedures and facilitate biomarker studies in disease models and patient samples. The new antibodies will not detect the very abundant normal alpha-synuclein present in brain, and can therefore single out the aggregate alpha-synuclein pathology of Parkinson’s.
Anticipated Outcome:
We anticipate the identification of optimal alpha-synuclein aggregate-specific antibodies that can then be distributed to the scientific community for investigation of disease mechanisms in Parkinson’s disease.