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Fibrillar form of α-synuclein-specific scFv antibody inhibits α-synuclein seeds induced aggregation and toxicity

Lookup NU author(s): Dr Daniel ErskineORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Synucleinopathies including Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are characterized by pathological accumulation of α-synuclein (α-syn). Amongst the various approaches attempting to tackle the pathological features of synucleinopathies, antibody-based immunotherapy holds much promise. However, the large size of antibodies and corresponding difficulty in crossing the blood-brain barrier has limited development in this area. To overcome this issue, we engineered single-chain variable fragments (scFvs) against fibrillar α-syn, a putative disease-relevant form of α-syn. The purified scFvs showed specific activity towards α-syn fibrils and oligomers in comparison to monomers and recognized intracellular inclusions in human post-mortem brain tissue of Lewy body disease cases, but not aged controls. In vitro studies indicated scFvs inhibit the seeding of α-syn aggregation in a time-dependent manner, decreased α-syn seed-induced toxicity in a cell model of PD, and reduced the production of insoluble α-syn phosphorylated at Ser-129 (pS129-α-syn). These results suggest that our α-syn fibril-specific scFvs recognize α-syn pathology and can inhibit the aggregation of α-syn in vitro and prevent seeding-dependent toxicity. Therefore, the scFvs described here have considerable potential to be utilized towards immunotherapy in synucleinopathies and may also have applications in ante-mortem imaging modalities.

Publication metadata

Author(s): Gupta V, Salim S, Hmila I, Vaikath NN, Sudhakaran IP, Ghanem SS, Majbour NK, Abdulla SA, Emara MM, Abdesselem HB, Lukacsovich T, Erskine D, El-Agnaf OMA

Publication type: Article

Publication status: Published

Journal: Scientific Reports

Year: 2020

Volume: 10

Print publication date: 18/05/2020

Online publication date: 18/05/2020

Acceptance date: 24/04/2020

Date deposited: 24/05/2020

ISSN (electronic): 2045-2322

Publisher: Nature Publishing Group


DOI: 10.1038/s41598-020-65035-8

PubMed id: 32424162


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Funder referenceFunder name
... part of the Brains for Dementia Research Project.
... to the Newcastle upon Tyne NHS Foundation Trust and Newcastle University, and by a grant from the Alzheimer’s Society and Alzheimer’s Research UK as ...
Dr. El-Agnaf’s laboratory was funded by Qatar Biomedical Research Institute under the Start-up Fund SF 2017–007
Newcastle Brain Tissue Resource is funded in part by a grant from the UK Medical Research Council, by NIHR Newcastle Biomedical Research Centre awarded ...