Ronald Melki, Team Protein misfolding and aggregation in neurodegenerative diseases, Neurodegenerative Diseases, CNRS

Prion-like propagation of alpha-synuclein assemblies and the molecular basis of distinct synucleinopathies

The aggregation of proteins within the central nervous system is deleterious and associated to neurodegenerative disorders. The aggregation of the protein alpha-synuclein is associated to synucleinopathies, in particular Parkinson's disease. How alpha-synuclein aggregates, how those aggregates traffic between cells, amplify by recruiting endogenous monomeric alpha-synuclein and cause distinct synucleinopathies is unclear.

I will explain the molecular events that lead to alpha-synuclein aggregation. I will present data illustrating the propagation properties of aggregated alpha-synuclein. I will show how alpha-synuclein aggregates bind to neurons cell membranes, what they bind to and the cellular consequences of binding. I will present quantitative assessment of their uptake, transport and export. I will show evidence that pathogenic alpha-synuclein aggregates disrupt the endolysosomal membranes, reach the cytosol where they amplify. Finally, I will describe how alpha-synuclein fibrillar polymorphs cause distinct diseases. I will finish by presenting strategies targeting the propagation of aggregated alpha-synuclein.

Host: Professor Daniel Otzen, iNANO & Dept. of Molecular Biology and Genetics, AU