The intracellular milieu of Parkinson’s disease patient brain cells modulates alpha-synuclein protein aggregation
Gustavsson, Nadja LU ; Savchenko, Ekaterina LU ; Klementieva, Oxana LU
and Roybon, Laurent
LU
(2021)
In Acta Neuropathologica Communications
9(1).
- 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... (More)
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.
(Less)
- author
- Gustavsson, Nadja
LU
; Savchenko, Ekaterina
LU
; Klementieva, Oxana
LU
and Roybon, Laurent
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha-synuclein, Cellular environment, Human iPSCs, Midbrain spheroids, Parkinson’s disease, Protein aggregation
- in
- Acta Neuropathologica Communications
- volume
- 9
- issue
- 1
- article number
- 153
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:34530929
- scopus:85115093588
- ISSN
- 2051-5960
- DOI
- 10.1186/s40478-021-01256-w
- language
- English
- LU publication?
- yes
- id
- 9a066171-5a8d-4281-942a-a64ade22728b
- date added to LUP
- 2021-10-01 12:17:55
- date last changed
- 2024-11-17 09:55:38
@article{9a066171-5a8d-4281-942a-a64ade22728b,
abstract = {{<p>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.</p>}},
author = {{Gustavsson, Nadja and Savchenko, Ekaterina and Klementieva, Oxana and Roybon, Laurent}},
issn = {{2051-5960}},
keywords = {{Alpha-synuclein; Cellular environment; Human iPSCs; Midbrain spheroids; Parkinson’s disease; Protein aggregation}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Acta Neuropathologica Communications}},
title = {{The intracellular milieu of Parkinson’s disease patient brain cells modulates alpha-synuclein protein aggregation}},
url = {{http://dx.doi.org/10.1186/s40478-021-01256-w}},
doi = {{10.1186/s40478-021-01256-w}},
volume = {{9}},
year = {{2021}},
}