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Gamma-synuclein pathology in amyotrophic lateral sclerosis
OBJECTIVE: The prominent histopathological feature of the amyotrophic lateral sclerosis (ALS) is the presence of intracellular inclusions in degenerating neurons and their axons. The appearance and localization of these pathological structures depend on an aggregated protein that forms their scaffol...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BlackWell Publishing Ltd
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301672/ https://www.ncbi.nlm.nih.gov/pubmed/25642432 http://dx.doi.org/10.1002/acn3.143 |
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author | Peters, Owen M Shelkovnikova, Tatyana Highley, John Robin Cooper-Knock, Johnathan Hortobágyi, Tibor Troakes, Claire Ninkina, Natalia Buchman, Vladimir L |
author_facet | Peters, Owen M Shelkovnikova, Tatyana Highley, John Robin Cooper-Knock, Johnathan Hortobágyi, Tibor Troakes, Claire Ninkina, Natalia Buchman, Vladimir L |
author_sort | Peters, Owen M |
collection | PubMed |
description | OBJECTIVE: The prominent histopathological feature of the amyotrophic lateral sclerosis (ALS) is the presence of intracellular inclusions in degenerating neurons and their axons. The appearance and localization of these pathological structures depend on an aggregated protein that forms their scaffold. We investigated if γ-synuclein, an aggregation-prone protein highly expressed in healthy motor neurons, and predominantly localized in their axons and synaptic terminals is involved in ALS pathology. METHODS: Immunostaining of histological sections and sequential protein extraction from postmortem neural samples followed by immunoblotting. RESULTS: Immunohistochemical screening revealed a subset of sporadic (9 of 31) and familial (8 of 23) ALS cases with a novel type of pathology characterized by the accumulation of γ-synuclein in distinct profiles within the dorsolateral column. Sequential fractionation of proteins from the spinal cord tissues revealed detergent-insoluble γ-synuclein species specifically in the dorsolateral corticospinal tracts of a ALS patient with γ-synuclein-positive profiles in this region. These profiles are negative for protein markers commonly found in pathological inclusions in the spinal cord of ALS patients and most probably represent degenerated axons of upper motor neurons that have lost their neurofilaments. A subset of these profiles was found in association with phagocytic cells positive for Mac-2/Galectin-3. A smaller subset of studied ALS cases (4 of 54) contained large cytoplasmic inclusions in the cell body of remaining spinal motor neurons. INTERPRETATION: Our observations suggest that pathological aggregation of γ-synuclein might contribute to the pathogenesis of ALS. |
format | Online Article Text |
id | pubmed-4301672 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BlackWell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-43016722015-01-30 Gamma-synuclein pathology in amyotrophic lateral sclerosis Peters, Owen M Shelkovnikova, Tatyana Highley, John Robin Cooper-Knock, Johnathan Hortobágyi, Tibor Troakes, Claire Ninkina, Natalia Buchman, Vladimir L Ann Clin Transl Neurol Research Articles OBJECTIVE: The prominent histopathological feature of the amyotrophic lateral sclerosis (ALS) is the presence of intracellular inclusions in degenerating neurons and their axons. The appearance and localization of these pathological structures depend on an aggregated protein that forms their scaffold. We investigated if γ-synuclein, an aggregation-prone protein highly expressed in healthy motor neurons, and predominantly localized in their axons and synaptic terminals is involved in ALS pathology. METHODS: Immunostaining of histological sections and sequential protein extraction from postmortem neural samples followed by immunoblotting. RESULTS: Immunohistochemical screening revealed a subset of sporadic (9 of 31) and familial (8 of 23) ALS cases with a novel type of pathology characterized by the accumulation of γ-synuclein in distinct profiles within the dorsolateral column. Sequential fractionation of proteins from the spinal cord tissues revealed detergent-insoluble γ-synuclein species specifically in the dorsolateral corticospinal tracts of a ALS patient with γ-synuclein-positive profiles in this region. These profiles are negative for protein markers commonly found in pathological inclusions in the spinal cord of ALS patients and most probably represent degenerated axons of upper motor neurons that have lost their neurofilaments. A subset of these profiles was found in association with phagocytic cells positive for Mac-2/Galectin-3. A smaller subset of studied ALS cases (4 of 54) contained large cytoplasmic inclusions in the cell body of remaining spinal motor neurons. INTERPRETATION: Our observations suggest that pathological aggregation of γ-synuclein might contribute to the pathogenesis of ALS. BlackWell Publishing Ltd 2015-01 2014-12-12 /pmc/articles/PMC4301672/ /pubmed/25642432 http://dx.doi.org/10.1002/acn3.143 Text en © 2014 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Peters, Owen M Shelkovnikova, Tatyana Highley, John Robin Cooper-Knock, Johnathan Hortobágyi, Tibor Troakes, Claire Ninkina, Natalia Buchman, Vladimir L Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title | Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title_full | Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title_fullStr | Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title_full_unstemmed | Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title_short | Gamma-synuclein pathology in amyotrophic lateral sclerosis |
title_sort | gamma-synuclein pathology in amyotrophic lateral sclerosis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301672/ https://www.ncbi.nlm.nih.gov/pubmed/25642432 http://dx.doi.org/10.1002/acn3.143 |
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