eprintid: 10144750
rev_number: 6
eprint_status: archive
userid: 699
dir: disk0/10/14/47/50
datestamp: 2022-03-08 11:39:52
lastmod: 2022-03-08 11:39:52
status_changed: 2022-03-08 11:39:52
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Sonustun, Berkiye
creators_name: Altay, Melek Firat
creators_name: Strand, Catherine
creators_name: Ebanks, Kirsten
creators_name: Hondhamuni, Geshanthi
creators_name: Warner, Thomas T
creators_name: Lashuel, Hilal A
creators_name: Bandopadhyay, Rina
title: Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy
ispublished: pub
divisions: C07
divisions: F84
divisions: B02
divisions: UCL
divisions: D07
keywords: alpha-synuclein; post-translational modifications; Parkinson’s disease; multiple system atrophy; Lewy bodies; Lewy neurites; glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry
note: © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
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Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
abstract: 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.
date: 2022-03-06
date_type: published
publisher: MDPI AG
official_url: https://doi.org/10.3390/cells11050906
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1943754
doi: 10.3390/cells11050906
lyricists_name: Bandopadhyay, Rina
lyricists_id: RBAND40
actors_name: Bandopadhyay, Rina
actors_id: RBAND40
actors_role: owner
full_text_status: public
publication: Cells
volume: 11
number: 5
article_number: 906
issn: 2073-4409
citation:        Sonustun, Berkiye;    Altay, Melek Firat;    Strand, Catherine;    Ebanks, Kirsten;    Hondhamuni, Geshanthi;    Warner, Thomas T;    Lashuel, Hilal A;           Sonustun, Berkiye;  Altay, Melek Firat;  Strand, Catherine;  Ebanks, Kirsten;  Hondhamuni, Geshanthi;  Warner, Thomas T;  Lashuel, Hilal A;  Bandopadhyay, Rina;   - view fewer <#>    (2022)    Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson’s Disease and Multiple System Atrophy.                   Cells , 11  (5)    , Article 906.  10.3390/cells11050906 <https://doi.org/10.3390/cells11050906>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10144750/1/cells-11-00906.pdf