[S-07-1] Alpha-synuclein aggregates polymorphism and the molecular basis of diverse synucleinopathies
Ronald Melki is Director of Research at French National Center for Scientific Research since 2000. He chaired several Institutes in France (over 700 scientists) and is recipient of several awards, among which the Grand Prize of the French Academy. He has been characterizing the aggregation process of infectious proteins since 1999. He demonstrated that Huntingtin and alpha-synuclein aggregates propagate from affected to healthy neighbor cells. He identified the most toxic Huntingtin, tau and alpha-synuclein aggregates and documented their interaction with neuron membranes as well as their uptake and transport. He generated alpha-synuclein aggregates that differ structurally and pathologically, establishing a structural-molecular basis for different synucleinopathies. His team amplified pathogenic alpha-synuclein and tau aggregates from patient brains and characterized them biochemically, biophysically, structurally and functionally in vitro and in vivo to unprecedented extent.
He assessed, with world leaders, the turnover, proteostatic response and traffic of pathogenic aggregates between neurons, astrocytes and microglia, revolutionizing the field by showing redistribution of pathogenic alpha-synuclein load among neuronal cells through intercellular connections during their processing. He mapped the surfaces of fibrillar alpha-synuclein and tau and solved the structure of alpha-synuclein fibrils amplified from patient brains at atomic resolution to design therapeutic and diagnostic tools.
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