Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_36AEA1313356
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Revisiting the specificity and ability of phospho-S129 antibodies to capture alpha-synuclein biochemical and pathological diversity.
Périodique
NPJ Parkinson's disease
Auteur⸱e⸱s
Lashuel H.A., Mahul-Mellier A.L., Novello S., Hegde R.N., Jasiqi Y., Altay M.F., Donzelli S., DeGuire S.M., Burai R., Magalhães P., Chiki A., Ricci J., Boussouf M., Sadek A., Stoops E., Iseli C., Guex N.
ISSN
2373-8057 (Print)
ISSN-L
2373-8057
Statut éditorial
Publié
Date de publication
20/10/2022
Peer-reviewed
Oui
Volume
8
Numéro
1
Pages
136
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Antibodies against phosphorylated alpha-synuclein (aSyn) at S129 have emerged as the primary tools to investigate, monitor, and quantify aSyn pathology in the brain and peripheral tissues of patients with Parkinson's disease and other neurodegenerative diseases. Herein, we demonstrate that the co-occurrence of multiple pathology-associated C-terminal post-translational modifications (PTMs) (e.g., phosphorylation at Tyrosine 125 or truncation at residue 133 or 135) differentially influences the detection of pS129-aSyn species by pS129-aSyn antibodies. These observations prompted us to systematically reassess the specificity of the most commonly used pS129 antibodies against monomeric and aggregated forms of pS129-aSyn in mouse brain slices, primary neurons, mammalian cells and seeding models of aSyn pathology formation. We identified two antibodies that are insensitive to pS129 neighboring PTMs. Although most pS129 antibodies showed good performance in detecting aSyn aggregates in cells, neurons and mouse brain tissue containing abundant aSyn pathology, they also showed cross-reactivity towards other proteins and often detected non-specific low and high molecular weight bands in aSyn knock-out samples that could be easily mistaken for monomeric or high molecular weight aSyn species. Our observations suggest that not all pS129 antibodies capture the biochemical and morphological diversity of aSyn pathology, and all should be used with the appropriate protein standards and controls when investigating aSyn under physiological conditions. Finally, our work underscores the need for more pS129 antibodies that are not sensitive to neighboring PTMs and more thorough characterization and validation of existing and new antibodies.
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/11/2022 9:12
Dernière modification de la notice
23/01/2024 7:23
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