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. 2022 Aug 30;25(9):1134–1148. doi: 10.1038/s41593-022-01140-3

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© The Author(s) 2022, corrected publication 2022

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Fig. 8 — Graphical illustration showing how α-Syn monomers form aggregates inside neurons and induce cell toxicity. Monomeric α-Syn is taken up in neurons where it begins to self-assemble first into a population of amorphous, loosely ordered oligomeric species, which progress to form highly ordered oligomeric species. Aggregates form with a dense central core of highly ordered oligomers surrounded by a rim of loosely packed oligomers and occur in multiple hotspots throughout the cell body, including the nucleus, Golgi, vesicles and mitochondria. Mitochondria are a critical site of aggregation due to the functional consequences: CL triggers oligomerization of A53T α-Syn. A53T α-Syn induces over-production of mROS, promoting oligomerization of α-Syn. A53T α-Syn oligomerization impairs complex I function and ATP production and promotes early opening of mPTP, leading to cell death.