Interfacial Aggregation of Alpha-Synuclein in Parkinson's Disease

Aggregation of a-synuclein (aSyn) in the human brain is a pathological hallmark of Parkinson's disease. aSyn carries no catalytic activity, and its function in the healthy brain remains unknown. However, the aggregation and fibrillization of aSyn lead to the formation of amyloids and permanent damage to the human brain. Parkinson's disease currently has no cure primarily due to the lack of knowledge on aSyn aggregation mechanism. Preliminary investigation revealed that aSyn aggregates when exposed to non-fluid hydrophobic interfaces or preformed seeds. Our research project further investigates what interfaces induce aSyn aggregation and fibrillization. We will prepare various hydrophobic interfaces by functionalizing custom quartz slides with silane coupling reagents. Circular Dichroism (CD) spectra will be recorded using Chirascan CD Spectrophotometer located at the Montclair State University (MSU). Collected data will be deconvoluted, and changes in the secondary structure of aSyn analyzed using both DichroWeb online portal provided by the University of London, UK and the CDtoolX software available in a chemistry computer lab, MSU. Our research project will provide the foundations for further investigation of aSyn aggregation mechanism, and identification of interfacial molecular analogs in the human brain, such as lipids, nucleic acids, and cell lysates. Knowledge of aSyn pathological pathways can provide new opportunities for pharmaceutical intervention at the early stages of Parkinson's disease.