TY  - JOUR
N2  - Aggregated alpha-synuclein (?-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 ?-synuclein exist, including phosphorylated and nitrated forms. It is unclear which ?-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant ?-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three ?-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 ?-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 ?-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 ?-synuclein in MSA. Quantification of the LB scores revealed that pS129 ?-synuclein was the dominant and earliest ?-synuclein PTM, followed by nY39 ?-synuclein, while lower amounts of pSer87 ?-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.
IS  - 5
VL  - 11
PB  - MDPI AG
A1  - Sonustun, Berkiye
A1  - Altay, Melek Firat
A1  - Strand, Catherine
A1  - Ebanks, Kirsten
A1  - Hondhamuni, Geshanthi
A1  - Warner, Thomas T
A1  - Lashuel, Hilal A
A1  - Bandopadhyay, Rina
Y1  - 2022/03/06/
ID  - discovery10144750
SN  - 2073-4409
N1  - © 2022 by the authors.
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/).
JF  - Cells
AV  - public
UR  - https://doi.org/10.3390/cells11050906
TI  - Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson?s Disease and Multiple System Atrophy
KW  - alpha-synuclein; post-translational modifications; Parkinson?s disease; multiple system atrophy; Lewy bodies; Lewy neurites; glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry
ER  -