Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions
Liu, Di LU ; Guo, Jian Jun ; Su, Ji Hui ; Svanbergsson, Alexander LU
; Yuan, Lin
; Haikal, Caroline
LU
; Li, Wen
LU
; Gouras, Gunnar
LU
and Li, Jia Yi
LU
(2021)
In Translational Neurodegeneration
10.
- Abstract
Background: Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of... (More)
Background: Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods: Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results: The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions: The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.
(Less)
- author
- Liu, Di
LU
; Guo, Jian Jun
; Su, Ji Hui
; Svanbergsson, Alexander
LU
; Yuan, Lin
; Haikal, Caroline
LU
; Li, Wen
LU
; Gouras, Gunnar
LU
and Li, Jia Yi
LU
- organization
- publishing date
- 2021-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Parkinson’s disease, Prion-like propagation, Strains, α-Synuclein
- in
- Translational Neurodegeneration
- volume
- 10
- article number
- 20
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:34148543
- scopus:85108200146
- ISSN
- 2047-9158
- DOI
- 10.1186/s40035-021-00242-5
- language
- English
- LU publication?
- yes
- additional info
- Funding Information: Financial supports of JYL lab by the National Key Research and Development Program of China (2018YFA0108500), the National Natural Science Foundation (81430025, 81701265, 31800898, U1801681), and the Key Field Research Development Program of Gungdong Province (2018B030337001). Financial supports of JYL lab by the Swedish Research Council (521–2014-3257, 2019–01551), EU-JPND (aSynProtec) and EU-JPND (REfrAME), EU H2020-MSCA-ITN-2016 (Syndegen), the Strong Research Environment MultiPark (Multidisciplinary research on Parkinson’s disease), Parkinsonfonden and Olle Engkvist Byggmästare Foundation. DL was supported by China Scholarship Council. Open Access funding provided by Lund University. Funding Information: We thank Sheng Yang (College of Life and Health Sciences, Northeastern University, China) for the help of behavioral tests. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
- id
- 50232a0f-f2fd-44a3-8352-9a3b144f699c
- date added to LUP
- 2021-06-26 21:53:55
- date last changed
- 2024-06-15 12:57:51
@article{50232a0f-f2fd-44a3-8352-9a3b144f699c,
abstract = {{<p>Background: Accumulation of alpha-synuclein (α-syn) is a main pathological hallmark of Parkinson’s and related diseases, which are collectively known as synucleinopathies. Growing evidence has supported that the same protein can induce remarkably distinct pathological progresses and disease phenotypes, suggesting the existence of strain difference among α-syn fibrils. Previous studies have shown that α-syn pathology can propagate from the peripheral nervous system (PNS) to the central nervous system (CNS) in a “prion-like” manner. However, the difference of the propagation potency from the periphery to CNS among different α-syn strains remains unknown and the effect of different generation processes of these strains on the potency of seeding and propagation remains to be revealed in more detail. Methods: Three strains of preformed α-syn fibrils (PFFs) were generated in different buffer conditions which varied in pH and ionic concentrations. The α-syn PFFs were intramuscularly (IM) injected into a novel bacterial artificial chromosome (BAC) transgenic mouse line that expresses wild-type human α-syn, and the efficiency of seeding and propagation of these PFFs from the PNS to the CNS was evaluated. Results: The three strains of α-syn PFFs triggered distinct propagation patterns. The fibrils generated in mildly acidic buffer led to the most severe α-syn pathology, degeneration of motor neurons and microgliosis in the spinal cord. Conclusions: The different α-syn conformers generated in different conditions exhibited strain-specific pathology and propagation patterns from the periphery to the CNS, which further supports the view that α-syn strains may be responsible for the heterogeneity of pathological features and disease progresses among synucleinopathies.</p>}},
author = {{Liu, Di and Guo, Jian Jun and Su, Ji Hui and Svanbergsson, Alexander and Yuan, Lin and Haikal, Caroline and Li, Wen and Gouras, Gunnar and Li, Jia Yi}},
issn = {{2047-9158}},
keywords = {{Parkinson’s disease; Prion-like propagation; Strains; α-Synuclein}},
language = {{eng}},
publisher = {{BioMed Central (BMC)}},
series = {{Translational Neurodegeneration}},
title = {{Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions}},
url = {{http://dx.doi.org/10.1186/s40035-021-00242-5}},
doi = {{10.1186/s40035-021-00242-5}},
volume = {{10}},
year = {{2021}},
}