A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease
Date
2022
Authors
Bérard, Morgan
Sheta, Razan
Malvaut, Sarah
Rodriguez-Aller, Raquel
Teixeira, Maxime
Idi, Walid
Turmel, Roxanne
Alpaugh, Melanie
Dubois, Marilyn
Dahmene, Manel
Journal Title
Journal ISSN
Volume Title
Publisher
PLoS Biology
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.
Description
We would like to thank Ms. Frédérique Larroquette from McGill University for her technical assistance.
Keywords
neurons, dopaminergics, protein aggregation, midbrain, optogenetics, transfection, neostriatum, confocal microscopy
Citation
Bérard, M., Sheta, R., Malvaut, S., Rodriguez-Aller, R., Teixeira, M., Idi, W., ... Oueslati, A. (2022). A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease. PLoS Biology, 20(3), e3001578. https://doi.org/10.1371/journal.pbio.3001578