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Implication of α-synuclein prion-like propagation in Parkinson's disease pathogenesis 

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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by severe motor and cognitive symptoms and by the massive loss of vulnerable neuronal population in the brain. Beside the neuronal damage, PD is characterized by the formation of intra-neuronal aggregates called Lewy bodies. These fibrillar inclusions are mainly constituted of a presynaptic protein, α-synuclein. Increasing body of evidences from neuropathological, animal models and in vitro studies, suggests that α-synuclein spreads from one brain region to another via prion-like mechanisms. This prion-like behavior has emerged as a new modulator of α-synuclein toxicity and may contribute to the disease progression.

The general aim of our project is to decorticate the cellular and molecular bases of α-synuclein prion-like propagation. More specifically we will seek to:

1. Create a new cellular and animal model of α-synuclein spreading.

2. Identify and characterize the authentic α-synuclein pion-like strains.

The expected results will enable us to bring new insight into the etiology of PD and how the disease starts and progresses. Moreover, the cellular and animal model of α-synuclein propagation will help us identify the pathogenic α-synuclein prion-like strains and it will offer a unique opportunity to develop new therapeutic strategies to halt or slow down the progression of PD.