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- W3113296970 abstract "• Human alpha-synuclein pre-formed fibrils (a-syn PFFs) were disseminated to the bilateral hemisphere 6 h post-injection. • Disseminated a-syn PFFs were associated with proteins linked to “neuronal system” and “vesicle-mediated transport”. • Disseminated Quantum dots-labeled a-syn PFFs from the inoculated site to the contralateral side mainly localized in synapses. The pathological form of a-synuclein (a-syn) is transmitted through neural circuits in the brains of Parkinson disease (PD) patients and amplifies misfolded a-syn, further forming intracellular deposits. However, the details of a-syn pre-formed fibrils (PFFs) transmission in vivo have not been fully elucidated. By inoculating Quantum dots (QD)-labeled a-syn PFFs (QD-a-syn PFFs) into the unilateral striatum, we detected QD-a-syn PFFs in brain homogenates obtained from the ipsilateral and contralateral sides of the inoculated site and further obtained QD-a-syn PFFs enriched-particles with fluorescence-activated organelle sorting. Proteomic analysis suggested that QD-a-syn PFFs-enriched particles in the contralateral side were associated with component proteins of synapse. In contrast, QD-a-syn PFFs-enriched particles in the ipsilateral side were associated with proteins belonging to ER components. Immunostaining of brain sections confirmed that QD-a-syn PFFs in the contralateral side were co-localized with synaptic vesicle marker proteins in the cortex and striatum. Additionally, QD-a-syn PFFs in the ipsilateral side were more co-localized with ER marker proteins compared to the contralateral side. These results correspond to proteomic analysis. This study provides potential candidates for the subcellular localization of a-syn PFFs in vivo during the dissemination phase of seeds. These subcellular compartments could be involved in the transmission of seeds." @default.
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- W3113296970 date "2021-09-01" @default.
- W3113296970 modified "2023-10-12" @default.
- W3113296970 title "Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds" @default.
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- W3113296970 doi "https://doi.org/10.1016/j.neures.2020.11.009" @default.
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