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Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients
In Parkinson’s disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been spec...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806361/ https://www.ncbi.nlm.nih.gov/pubmed/29422109 http://dx.doi.org/10.1186/s40478-018-0509-1 |
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author | Recasens, Ariadna Carballo-Carbajal, Iria Parent, Annabelle Bové, Jordi Gelpi, Ellen Tolosa, Eduardo Vila, Miquel |
author_facet | Recasens, Ariadna Carballo-Carbajal, Iria Parent, Annabelle Bové, Jordi Gelpi, Ellen Tolosa, Eduardo Vila, Miquel |
author_sort | Recasens, Ariadna |
collection | PubMed |
description | In Parkinson’s disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0509-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5806361 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58063612018-02-15 Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients Recasens, Ariadna Carballo-Carbajal, Iria Parent, Annabelle Bové, Jordi Gelpi, Ellen Tolosa, Eduardo Vila, Miquel Acta Neuropathol Commun Research In Parkinson’s disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s40478-018-0509-1) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-08 /pmc/articles/PMC5806361/ /pubmed/29422109 http://dx.doi.org/10.1186/s40478-018-0509-1 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Recasens, Ariadna Carballo-Carbajal, Iria Parent, Annabelle Bové, Jordi Gelpi, Ellen Tolosa, Eduardo Vila, Miquel Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title | Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title_full | Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title_fullStr | Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title_full_unstemmed | Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title_short | Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson’s disease patients |
title_sort | lack of pathogenic potential of peripheral α-synuclein aggregates from parkinson’s disease patients |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806361/ https://www.ncbi.nlm.nih.gov/pubmed/29422109 http://dx.doi.org/10.1186/s40478-018-0509-1 |
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