| Autor: |
Martin Lévesque, Edward A. Fon, Francesca Cicchetti, Thomas M. Durcan, Charleen Salesse, Sarah Malvaut, Omid Tavassoly, Marilyn Dubois, Walid Idi, Jérôme Lamontagne-Proulx, Raquel Rodriguez-Aller, Wen Luo, Abid Oueslati, Marie-Ève Tremblay, Maxime Teixeira, Morgan Bérard, Raza Qazi, Marie-Kim St-Pierre, Jae-Woong Jeong, Esther Del Cid-Pellitero, Razan Sheta, Denis Soulet, Roxanne Turmel, Manel Dahmene, Melanie Alpaugh, Luc Vallières, Armen Saghatelyan |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| Popis: |
α-Synuclein (α-syn) aggregation into insoluble deposits, referred to as Lewy bodies (LBs), is the paramount pathological hallmark of Parkinson’s disease (PD) and related α-synucleinopathies. However, the mechanism by which these aggregates contribute to neurodegeneration remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of α-syn 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 real-time induction of α-syn inclusion formation with remarkable spatiotemporal resolution in living cells. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical and ultrastructural features of authentic LBs. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission and induce dopaminergic neuronal loss and PD-like behavioral impairment. Collectively, our findings provide a controllable tool that permits for the generation, visualization and dissection of the role of protein aggregation in neurodegeneration. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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