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Endogenous levels of alpha-synuclein modulate seeding and aggregation in cultured cells

Abstract : Parkinson's disease is a progressive neurodegenerative disorder characterized by the accumulation of misfolded alphasynuclein 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.
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Contributor : Ronald Melki Connect in order to contact the contributor
Submitted on : Thursday, June 2, 2022 - 12:17:48 PM
Last modification on : Monday, August 8, 2022 - 5:38:05 PM
Long-term archiving on: : Saturday, September 3, 2022 - 6:07:55 PM

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Eftychia Vasili, Antonio Dominguez-Meijide, Manuel Flores-León, Mohammed Al-Azzani, Angeliki Kanellidi, et al.. Endogenous levels of alpha-synuclein modulate seeding and aggregation in cultured cells. Molecular Neurobiology, Humana Press, 2021, 59, pp.1273 - 1284. ⟨10.1007/s12035-021-02713-2⟩. ⟨cea-03683738⟩

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