Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds

Junya Kasahara, Yukio Imamura, Akiko Hiyama, Tomoyuki Yamanaka, Haruko Miyazaki, Nobuyuki Nukina

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)341-349
Number of pages9
JournalNeuroscience Research
Volume170
DOIs
Publication statusPublished - Sep 2021
Externally publishedYes

Keywords

  • Fluorescence-activated organelle sorting
  • Pre-formed fibril
  • Quantum dot
  • Rapid dissemination
  • Subcellular fractionation.
  • Synapse

ASJC Scopus subject areas

  • Neuroscience(all)

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