Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells
2022 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Endogenous Levels of Alpha-Synuclein Modulate Seeding and Aggregation in Cultured Cells
Vasili, E.; Dominguez-Meijide, A.; Flores-León, M.; Al-Azzani, M.; Kanellidi, A.; Melki, R. & Stefanis, L. et al. (2022)
Molecular Neurobiology,. DOI: https://doi.org/10.1007/s12035-021-02713-2
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Details
- Authors
- Vasili, Eftychia; Dominguez-Meijide, Antonio; Flores-León, Manuel; Al-Azzani, Mohammed; Kanellidi, Angeliki; Melki, Ronald; Stefanis, Leonidas; Outeiro, Tiago Fleming
- 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.
- Issue Date
- 2022
- Journal
- Molecular Neurobiology
- Project
- EXC 2067: Multiscale Bioimaging
SFB 1286: Quantitative Synaptologie
SFB 1286 | B08: Definition von Kaskaden molekularer Veränderungen bei Synucleinopathien während der Neurodegeneration - Working Group
- RG Outeiro (Experimental Neurodegeneration)
- ISSN
- 0893-7648
- eISSN
- 1559-1182
- Language
- English