Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions
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...
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doaj-d21ca8e3605041a2942af645f2e6d2d22021-06-27T11:47:44ZengBMCTranslational Neurodegeneration2047-91582021-06-0110111510.1186/s40035-021-00242-5Differential seeding and propagating efficiency of α-synuclein strains generated in different conditionsDi Liu0Jian-Jun Guo1Ji-Hui Su2Alexander Svanbergsson3Lin Yuan4Caroline Haikal5Wen Li6Gunnar Gouras7Jia-Yi Li8Institute of Neuroscience, College of Life and Health Sciences, Northeastern UniversityInstitute of Neuroscience, College of Life and Health Sciences, Northeastern UniversityInstitute of Health Sciences, China Medical UniversityNeural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund UniversityInstitute of Health Sciences, China Medical UniversityNeural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund UniversityNeural Plasticity and Repair Unit, Wallenberg Neuroscience Center, Lund UniversityExperimental Dementia Research, Lund UniversityInstitute of Neuroscience, College of Life and Health Sciences, Northeastern UniversityAbstract 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.https://doi.org/10.1186/s40035-021-00242-5α-SynucleinStrainsPrion-like propagationParkinson’s disease |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan Caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li |
spellingShingle |
Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan Caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions Translational Neurodegeneration α-Synuclein Strains Prion-like propagation Parkinson’s disease |
author_facet |
Di Liu Jian-Jun Guo Ji-Hui Su Alexander Svanbergsson Lin Yuan Caroline Haikal Wen Li Gunnar Gouras Jia-Yi Li |
author_sort |
Di Liu |
title |
Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
title_short |
Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
title_full |
Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
title_fullStr |
Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
title_full_unstemmed |
Differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
title_sort |
differential seeding and propagating efficiency of α-synuclein strains generated in different conditions |
publisher |
BMC |
series |
Translational Neurodegeneration |
issn |
2047-9158 |
publishDate |
2021-06-01 |
description |
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 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. |
topic |
α-Synuclein Strains Prion-like propagation Parkinson’s disease |
url |
https://doi.org/10.1186/s40035-021-00242-5 |
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