Physics-Biology interface seminar: Ronald Melki

Prion-like propagation of alpha-synuclein assemblies in synucleinopathies, similarities with Tau in Tauopathies

Ronald Melki (Institut François Jacob, CEA & CNRS)

The aggregation of proteins within the central nervous system is deleterious and associated to neurodegenerative disorders. The aggregation of the proteins alpha-synuclein and Tau are associated to synucleinopathies, in particular Parkinson’s disease, and tauopathies, among which Alzheimer’s disease, respectively. How alpha-synuclein and Tau aggregates, how those aggregates traffic between cells, amplify by recruiting endogenous monomeric alpha-synuclein or Tau and cause distinct synucleinopathies or tauopathies is unclear.

I will explain the molecular events that lead to alpha-synuclein or Tau aggregation. I will show that alpha-synuclein and Tau aggregates bind to neurons cell membranes and explain the cellular consequences of binding. The similarities and differences between alpha-synuclein and Tau will be highlighted. I will explain how alpha-synuclein and Tau aggregates penetrate the cells and get transported. Finally, I will describe how the structure of the fibrillar polymorphs alpha-synuclein and Tau aggregation yield distinct diseases.

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