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Lookup NU author(s): Professor Tiago OuteiroORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 by the authors. Parkinson’s disease (PD) pathology is characterized by the loss of dopaminergic neurons of the nigrostriatal system and accumulation of Lewy bodies (LB) and Lewy neurites (LN), inclusions mainly composed of alpha-synuclein (α-Syn) fibrils. Studies linking the occurrence of mutations and multiplications of the α-Syn gene (SNCA) to the onset of PD support that α-Syn deposition may play a causal role in the disease, in line with the hypothesis that disease progression may correlate with the spreading of LB pathology in the brain. Interestingly, LB accumulate posttranslationally modified forms of α-Syn, suggesting that α-Syn posttranslational modifications impinge on α-Syn aggregation and/or toxicity. Here, we aimed at investigating changes in α-Syn phosphorylation, nitration and acetylation in mice subjected to nigral stereotaxic injections of adeno-associated viral vectors inducing overexpression of human α-Syn (AAV-hα-Syn), that model genetic PD with SNCA multiplications. We detected a mild increase of serine (Ser) 129 phosphorylated α-Syn in the substantia nigra (SN) of AAV-hα-Syn-injected mice in spite of the previously described marked accumulation of this PTM in the striatum. Following AAV-hα-Syn injection, tyrosine (Tyr) 125/136 nitrated α-Syn accumulation in the absence of general 3-nitrotirosine (3NT) or nitrated-Tyr39 α-Syn changes and augmented protein acetylation abundantly overlapping with α-Syn immunopositivity were also detected.
Author(s): Brembati V, Faustini G, Longhena F, Outeiro TF, Bellucci A
Publication type: Article
Publication status: Published
Journal: International Journal of Molecular Sciences
Year: 2023
Volume: 24
Issue: 17
Online publication date: 30/08/2023
Acceptance date: 27/08/2023
Date deposited: 18/09/2023
ISSN (print): 1661-6596
ISSN (electronic): 1422-0067
Publisher: MDPI
URL: https://doi.org/10.3390/ijms241713435
DOI: 10.3390/ijms241713435
Data Access Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to intellectual property restrictions.
PubMed id: 37686236
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