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@article{vasili_endogenous_2022,
title = {Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells},
volume = {59},
issn = {0893-7648, 1559-1182},
url = {https://link.springer.com/10.1007/s12035-021-02713-2},
doi = {10.1007/s12035-021-02713-2},
abstract = {Abstract
Parkinson’s disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alpha-synuclein in intraneuronal inclusions known as Lewy bodies and Lewy neurites. Multiple studies strongly implicate the levels of alpha-synuclein as a major risk factor for the onset and progression of Parkinson’s disease. Alpha-synuclein pathology spreads progressively throughout interconnected brain regions but the precise molecular mechanisms underlying the seeding of alpha-synuclein aggregation are still unclear. Here, using stable cell lines expressing alpha-synuclein, we examined the correlation between endogenous alpha-synuclein levels and the seeding propensity by exogenous alpha-synuclein preformed fibrils. We applied biochemical approaches and imaging methods in stable cell lines expressing alpha-synuclein and in primary neurons to determine the impact of alpha-synuclein levels on seeding and aggregation. Our results indicate that the levels of alpha-synuclein define the pattern and severity of aggregation and the extent of p-alpha-synuclein deposition, likely explaining the selective vulnerability of different cell types in synucleinopathies. The elucidation of the cellular processes involved in the pathological aggregation of alpha-synuclein will enable the identification of novel targets and the development of therapeutic strategies for Parkinson’s disease and other synucleinopathies.},
pages = {1273--1284},
number = {2},
journaltitle = {Molecular Neurobiology},
shortjournal = {Mol Neurobiol},
author = {Vasili, Eftychia and Dominguez-Meijide, Antonio and Flores-León, Manuel and Al-Azzani, Mohammed and Kanellidi, Angeliki and Melki, Ronald and Stefanis, Leonidas and Outeiro, Tiago Fleming},
urldate = {2022-04-13},
date = {2022-02},
langid = {english},
keywords = {peer-reviewed},
}