eprintid: 10142175
rev_number: 15
eprint_status: archive
userid: 608
dir: disk0/10/14/21/75
datestamp: 2023-06-23 11:07:58
lastmod: 2023-06-23 11:07:58
status_changed: 2023-06-23 11:07:58
type: working_paper
metadata_visibility: show
creators_name: Sonustun, B
creators_name: Altay, F
creators_name: Strand, C
creators_name: Hondhamuni, G
creators_name: Warner, T
creators_name: Lashuel, H
creators_name: Bandopadhyay, R
title: Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and Multiple System Atrophy
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F84
keywords: alpha-synuclein; post-translational modifications; Parkinson’s disease; Multiple
system atrophy; Lewy bodies; Lewy neurites; Glial cytoplasmic inclusions; phosphorylation;
nitration; immunohistochemistry
note: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: Aggregated alpha-synuclein (a-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), respectively. Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of a-synuclein exist, including phosphorylated and nitrated forms. It is unclear which a-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant a-synuclein PTMs in post-mortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three a-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology- affected regions of 15 PD, 5 MSA, 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 a-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures followed by nY39 a- synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 a- synuclein in MSA. Quantification of the LB scores revealed that pS129 a-synuclein was the dominant and earliest a-synuclein PTM followed by nY39 a-synuclein, while lower amounts of pSer87 a-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.
date: 2022-01
date_type: published
publisher: BioRXiv
official_url: https://doi.org/10.1101/2022.01.11.475823
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1915628
lyricists_name: Bandopadhyay, Rina
lyricists_name: Warner, Thomas
lyricists_id: RBAND40
lyricists_id: TTWAR25
actors_name: Bandopadhyay, Rina
actors_id: RBAND40
actors_role: owner
full_text_status: public
place_of_pub: Cold Spring Harbor, NY, USA
pages: 26
citation:        Sonustun, B;    Altay, F;    Strand, C;    Hondhamuni, G;    Warner, T;    Lashuel, H;    Bandopadhyay, R;      (2022)    Pathological relevance of post-translationally modified alpha-synuclein (pSer87, pSer129, nTyr39) in idiopathic Parkinson’s disease and Multiple System Atrophy.                    BioRXiv: Cold Spring Harbor, NY, USA.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10142175/1/BIORXIV-2022-475823v1-Bandopadhyay.pdf