Benjamin Dehay awarded by Parkinson’s Foundation

Benjamin Dehay (IMN – team Pathophysiology of proteinopathies) is one of the six Impact awardees of the Parkinson’s Foundation, with its project « Peripheral synucleinopathy: pathogenicity and modulation of propagation. »

With this project, in collaboration with Ariadna Laguna (Vall d’Hebron Research Institute, Barcelona) and Laura Parkkinen (Oxford Parkinson’s Disease Centre), he will characterize and compare alpha-synuclein aggregates from the brain and GI tract to improve understanding of Parkinson

Summary

Parkinson’s disease (PD) is a multisystem neurodegenerative disorder that is part of a group of diseases called synucleinopathies. One of the main cellular pathological hallmarks of PD is the formation of proteinaceous aggregates mainly composed of a-synuclein (a-Syn) protein inside the brain cells. It is now well established that a-Syn can misfold and aggregate into fibrillar species with a propensity to progressively and sequentially spread from affected to unaffected brain regions, thus invading the brain over the course of the disease. However, in Parkinson’s patients, a-Syn aggregates are not limited to the brain. Indeed, they are also found in the gastrointestinal (GI) tract possibly contributing to the occurrence of non-motor symptoms such as constipation, commonly experienced by patients with Parkinson’s. Overall, several questions remain open regarding where do these a-Syn aggregates originate, how do they progress from GI tract to the brain and vice versa, and why and how are they toxic to the cells that host them. Uncovering the different structures and biochemical properties of a-Syn aggregates in different vulnerable regions will improve our mechanistic understanding of the disease which is needed in order to find new molecules for therapeutic intervention. We propose and employ an integrated approach, using a panel of different biochemical and proteomic methods applied to human tissue to characterize and compare a-Syn aggregates derived from the brain and GI tract between control and PD patients. Then, we will assess how the human GI tract versus brain-derived a-Syn aggregates spread and become toxic over time by injecting them to different sites in old mice. Our ultimate ambition, using state-of-the-art technologies and unique human samples, and experimental expertise, is to provide for the first-time direct evidence of how GI tract- versus brain-derived a-Syn aggregates spread and become toxic in mice along the brain-gut axis.

About Parkinson’s foundation

https://www.parkinson.org/

The impact award funds innovative projects that are in need of support to see their maximum impact on the Parkinson’s community: https://www.parkinson.org/advancing-research/for-researchers/awards-independent-investigators