Unraveling the role of alpha-synuclein strains in the pathogenesis of Parkinson's disease and Multiple System Atrophy

Misfolded protein aggregates appear to be a common feature of several ageing-related neurodegenerative diseases. The major neuropathological hallmark in Parkinson's disease (PD) and related diseases such as Multiple System Atrophy (MSA) are alpha-synuclein protein deposits. We propose that different aggregated protein conformations or 'strains' are at the origin of the heterogeneous nature of the synucleinopathies. In this project we aim to further unravel several outstanding questions regarding the role of alpha-synuclein strains in PD and MSA. We can define the following objectives : 1.Develop and characterize a viral vector-based rodent model for MSA2.Characterize patient-derived alpha-synuclein strains in vivo3.Elucidate the role of the immune system in spreading and neurotoxicity of alpha-synuclein strainsA better understanding of the role of alpha-synuclein strains and neuroinflammation in alpha-synuclein-linked neurodegeneration will contribute to early diagnosis, prevention and the development of novel therapeutic strategies for synucleinopathies and other ageing-related disorders.

Keywords:Parkinson's disease, Multiple system atrophy, neurodegeneration, neuroinflammation, viral vector technology, animal model

Disciplines:Neurosciences, Biological and physiological psychology, Cognitive science and intelligent systems, Developmental psychology and ageing