(178f) Molecular Mechanisms for Self-Assembly in Neurodegenerative Diseases

Our research is aimed at developing a better understanding of some of the key chemical steps of this pathology and of other neurodegenerative diseases. The aggregation and fibrillation of a-synuclein, a brain protein of 140 residues, has been linked to several of these diseases, including Parkinson's and Alzheimer's diseases. Prior work has shown that this starts when a protein of a-synuclein undergoes a conformational change to form a partially folded intermediate. Several of these intermediates may then aggregate to form oligomers, amorphous aggregates or fibrils. The molecular mechanisms accounting for these phenomena are unknown. Understanding and analyzing these mechanisms is the goal of the proposed research. The aggregation and fibrillation of different proteins has been linked to several neurodegenerative diseases, including Parkinson's and Alzheimer's diseases. Prior work has shown that this starts when a protein undergoes a conformational change to form a partially folded intermediate. Several of these intermediates may then aggregate to form oligomers, amorphous aggregates or fibrils. We use molecular simulations to understand the molecular mechanisms accounting for these phenomena.