A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease.

TitleA light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease.
Publication TypeJournal Article
Year of Publication2022
AuteursBérard, M, Sheta, R, Malvaut, S, Rodriguez-Aller, R, Teixeira, M, Idi, W, Turmel, R, Alpaugh, M, Dubois, M, Dahmene, M, Salesse, C, Lamontagne-Proulx, J, St-Pierre, M-K, Tavassoly, O, Luo, W, Del Cid-Pellitero, E, Qazi, R, Jeong, J-W, Durcan, TM, Vallières, L, Tremblay, M-È, Soulet, D, Lévesque, M, Cicchetti, F, Fon, EA, Saghatelyan, A, Oueslati, A
JournalPLoS Biol
Volume20
Issue3
Paginatione3001578
Date Published2022 Mar
ISSN1545-7885
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.

DOI10.1371/journal.pbio.3001578
Alternate JournalPLoS Biol
PubMed ID35263320
PubMed Central IDPMC8936469