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Proteomic analysis of subcellular compartments containing disseminated alpha-synuclein seeds
- Source :
- Neuroscience Research. 170:341-349
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- Subjects :
- Proteomics
0301 basic medicine
animal diseases
Synaptic vesicle
Synapse
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
In vivo
Organelle
Humans
heterocyclic compounds
Alpha-synuclein
General Neuroscience
Brain
Parkinson Disease
General Medicine
Subcellular localization
nervous system diseases
Cortex (botany)
Cell biology
030104 developmental biology
nervous system
chemistry
alpha-Synuclein
health occupations
Synaptic Vesicles
030217 neurology & neurosurgery
Immunostaining
Subjects
Details
- ISSN :
- 01680102
- Volume :
- 170
- Database :
- OpenAIRE
- Journal :
- Neuroscience Research
- Accession number :
- edsair.doi.dedup.....5db56cb18f863631357afc5aa3aa6d7b