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Generation of monoclonal antibodies against phosphorylated α-Synuclein at serine 129: Research tools for synucleinopathies

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submitted on 2024-05-27, 06:05 and posted on 2024-05-27, 08:09 authored by Muneera Fayyad, Nour K. Majbour, Nishant N. Vaikath, Daniel Erskine, Heba El-Tarawneh, Indulekha P. Sudhakaran, Houari Abdesselem, Omar M.A. El-Agnaf

The majority of α-synuclein (α-syn) within Lewy bodies (LBs) has been reported to be phosphorylated at serine 129 (pS129-α-syn), suggesting a central role for phosphorylation in the pathogenesis of Parkinson’s disease (PD) and related synucleinopathies. Various studies have investigated the effect of α-syn phosphorylation but have failed to reach a consensus as to whether this modification accelerates or inhibits α-syn aggregation. Nevertheless, pS129-α-syn is a reliable marker of α-syn aggregates and is widely evaluated in biomarkers and post-mortem studies. While several antibodies specific for pS129-α-syn exist, their reactivity with non-specific antigens appears to be a common challenge. To gain valuable insights into the role of α-syn phosphorylation in disease pathogenesis, antibodies that are highly specific to pS129-α-syn are necessary. In this study, we describe the generation of three mouse monoclonal antibodies (mAbs; 5B9, 6H5 and 9G1) using hybridoma technology. These were thoroughly characterized and validated in combination with our previously generated mAb (PS129), and the commercial ab51253 (Abcam). We demonstrated that our mAbs are highly specific for pS129-α-syn and do not cross react with wild-type α-syn. Results from staining of post-mortem human brain tissue showed that our mAbs detect pS129-α-syn pathology in patients with synucleinopathies. This study highlights three new antibodies as excellent and highly specific research tools to explore the role of pS129-α-syn inclusions in synucleinopathies.

Other Information

Published in: Neuroscience Letters
License: http://creativecommons.org/licenses/by-nc-nd/4.0/
See article on publisher's website: https://dx.doi.org/10.1016/j.neulet.2020.134899

Funding

Qatar National Research Fund (NPRP8-517-3-112), Application of conformation-specific antibodies toward biomarker development for Parkinson’s disease.

Qatar National Research Fund (NPRP9-213-1- 043), Development of Novel Diagnostic and Therapeutic Tools for Parkinson's Diseases and Related Disorders.

History

Language

  • English

Publisher

Elsevier

Publication Year

  • 2020

License statement

This Item is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Institution affiliated with

  • Hamad Bin Khalifa University
  • College of Health and Life Sciences - HBKU
  • Qatar Biomedical Research Institute - HBKU
  • Neurological Disorders Research Center - QBRI
  • Weill Cornell Medicine - Qatar

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