| Literature DB >> 35263320 |
Morgan Bérard1,2, Razan Sheta1,2, Sarah Malvaut3,4, Raquel Rodriguez-Aller1,2,3, Maxime Teixeira1,2, Walid Idi1,2, Roxanne Turmel1,2, Melanie Alpaugh1,4, Marilyn Dubois1,2, Manel Dahmene1,2, Charleen Salesse3,4, Jérôme Lamontagne-Proulx1,5, Marie-Kim St-Pierre1,2, Omid Tavassoly6, Wen Luo6,7, Esther Del Cid-Pellitero6,7, Raza Qazi8, Jae-Woong Jeong8,9, Thomas M Durcan6,7, Luc Vallières1,2, Marie-Eve Tremblay1,2,10, Denis Soulet1,5, Martin Lévesque3,4, Francesca Cicchetti1,4, Edward A Fon6,7, Armen Saghatelyan3,4, Abid Oueslati1,2.
Abstract
Neurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.Entities:
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Year: 2022 PMID： 35263320 PMCID： PMC8936469 DOI： 10.1371/journal.pbio.3001578
Source DB: PubMed Journal: PLoS Biol ISSN： 1544-9173 Impact factor: 8.029