Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds. (September 2021)

• Record Type: Journal Article
• Authors: Kasahara, Junya; Imamura, Yukio; Hiyama, Akiko; Yamanaka, Tomoyuki; Miyazaki, Haruko; Nukina, Nobuyuki
• Is Part Of: Neuroscience research. Volume 170(2021)
• Page Start: 341
• Page End: 349
• Publication Date: 2021-09
• Subjects: PD Parkinson disease -- DLB dementia with Lewy bodies a-syn -- WT Alpha-synuclein WT -- PFFs wild type -- PFFs pre-formed fibrils QD-a-syn -- GO Quantum dots-labeled a-syn pre-formed fibrils -- FAOS Gene ontology -- ips fluorescence-activated organelle sorting -- ips ilateral side -- co contralateral side; Pre-formed fibril -- Quantum dot -- Rapid dissemination -- Synapse -- Fluorescence-activated organelle sorting -- Subcellular fractionation.; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2020.11.009
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: 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. Abstract: 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.