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Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy
Aggregated alpha-synuclein (α-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909017/ https://www.ncbi.nlm.nih.gov/pubmed/35269528 http://dx.doi.org/10.3390/cells11050906 |
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author | Sonustun, Berkiye Altay, Melek Firat Strand, Catherine Ebanks, Kirsten Hondhamuni, Geshanthi Warner, Thomas T. Lashuel, Hilal A. Bandopadhyay, Rina |
author_facet | Sonustun, Berkiye Altay, Melek Firat Strand, Catherine Ebanks, Kirsten Hondhamuni, Geshanthi Warner, Thomas T. Lashuel, Hilal A. Bandopadhyay, Rina |
author_sort | Sonustun, Berkiye |
collection | PubMed |
description | Aggregated alpha-synuclein (α-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of α-synuclein exist, including phosphorylated and nitrated forms. It is unclear which α-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant α-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three α-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 IPD cases, 5 MSA cases, and 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 α-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 α-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 α-synuclein in MSA. Quantification of the LB scores revealed that pS129 α-synuclein was the dominant and earliest α-synuclein PTM, followed by nY39 α-synuclein, while lower amounts of pSer87 α-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments. |
format | Online Article Text |
id | pubmed-8909017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-89090172022-03-11 Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy Sonustun, Berkiye Altay, Melek Firat Strand, Catherine Ebanks, Kirsten Hondhamuni, Geshanthi Warner, Thomas T. Lashuel, Hilal A. Bandopadhyay, Rina Cells Article Aggregated alpha-synuclein (α-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson’s disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of α-synuclein exist, including phosphorylated and nitrated forms. It is unclear which α-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant α-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three α-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 IPD cases, 5 MSA cases, and 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 α-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 α-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 α-synuclein in MSA. Quantification of the LB scores revealed that pS129 α-synuclein was the dominant and earliest α-synuclein PTM, followed by nY39 α-synuclein, while lower amounts of pSer87 α-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments. MDPI 2022-03-06 /pmc/articles/PMC8909017/ /pubmed/35269528 http://dx.doi.org/10.3390/cells11050906 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sonustun, Berkiye Altay, Melek Firat Strand, Catherine Ebanks, Kirsten Hondhamuni, Geshanthi Warner, Thomas T. Lashuel, Hilal A. Bandopadhyay, Rina Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title | Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title_full | Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title_fullStr | Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title_full_unstemmed | Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title_short | Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy |
title_sort | pathological relevance of post-translationally modified alpha-synuclein (pser87, pser129, ntyr39) in idiopathic parkinson’s disease and multiple system atrophy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8909017/ https://www.ncbi.nlm.nih.gov/pubmed/35269528 http://dx.doi.org/10.3390/cells11050906 |
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