CONICET | Buscador de Institutos y Recursos Humanos

The misfolding of proteins into a toxic conformation is proposed to be at the molecular foundation of a number of neurodegenerative disorders including Alzheimer and Parkinson?s disease. One common and defining feature of protein misfolding diseases is the formation and deposition of amyloid-like fibrils. The aggregation of the protein alpha-synuclein (AS) is a critical step in the etiology of Parkinson?s disease (PD) and other neurodegenerative synucleinopathies. The study of the structural and toxic mechanisms related to AS amyloid formation is critical to advance in the design of a therapeutic strategy. The identification of aggregation inhibitors and the investigation of their mechanism of action are fundamental in the quest to mitigate the pathological consequences of amyloid formation. By the combined application of a battery biochemical and biophysical tools we have addressed structural and molecular unresolved details related to the mechanistic rules that direct the anti-amyloid effect of small molecules on AS amyloid fibril formation.