Bibliographic Details
| Title: |
The intracellular milieu of Parkinson’s disease patient brain cells modulates alpha-synuclein protein aggregation |
| Authors: |
Nadja Gustavsson, Ekaterina Savchenko, Oxana Klementieva, Laurent Roybon |
| Source: |
Acta Neuropathologica Communications, Vol 9, Iss 1, Pp 1-6 (2021) |
| Publisher Information: |
BMC, 2021. |
| Publication Year: |
2021 |
| Collection: |
LCC:Neurology. Diseases of the nervous system |
| Subject Terms: |
Parkinson’s disease, Protein aggregation, Alpha-synuclein, Cellular environment, Human iPSCs, Midbrain spheroids, Neurology. Diseases of the nervous system, RC346-429 |
| More Details: |
Abstract Recent studies suggest that brain cell type specific intracellular environments may play important roles in the generation of structurally different protein aggregates that define neurodegenerative diseases. Using human induced pluripotent stem cells (hiPSC) and biochemical and vibrational spectroscopy techniques, we studied whether Parkinson’s disease (PD) patient genomes could modulate alpha-synuclein (aSYN) protein aggregates formation. We found increased β-sheets and aggregated aSYN in PD patient hiPSC-derived midbrain cells, compared to controls. Importantly, we discovered that aSYN protein aggregation is modulated by patient brain cells’ intracellular milieus at the primary nucleation phase. Additionally, we found changes in the formation of aSYN fibrils when employing cellular extracts from familial PD compared to idiopathic PD, in a Thioflavin T-based fluorescence assay. The data suggest that changes in cellular milieu induced by patient genomes trigger structural changes of aSYN potentially leading to the formation of strains having different structures, properties and seeding propensities. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2051-5960 |
| Relation: |
https://doaj.org/toc/2051-5960 |
| DOI: |
10.1186/s40478-021-01256-w |
| Access URL: |
https://doaj.org/article/53851b3c6282414381aae42ec9308475 |
| Accession Number: |
edsdoj.53851b3c6282414381aae42ec9308475 |
| Database: |
Directory of Open Access Journals |
