α-Synuclein Penetrates Mucin Hydrogels despite Its Mucoadhesive Properties

Matthias Marczynski, Carolin A. Rickert, Slav A. Semerdzhiev, Wouter R. Van Dijk, Ine M.J. Segers-Nolten, Mireille M.A.E. Claessens, Oliver Lieleg*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

Recent research indicates that the progression of Parkinson's disease can start from neurons of the enteric nervous system, which are in close contact with the gastrointestinal epithelium: α-synuclein molecules can be transferred from these epithelial cells in a prion-like fashion to enteric neurons. Thin mucus layers constitute a defense line against the exposure of noninfected cells to potentially harmful α-synuclein species. We show that - despite its mucoadhesive properties - α-synuclein can translocate across mucin hydrogels, and this process is accompanied by structural rearrangements of the mucin molecules within the gel. Penetration experiments with different α-synuclein variants and synthetic peptides suggest that two binding sites on α-synuclein are required to accomplish this rearrangement of the mucin matrix. Our results support the notion that the translocation of α-synuclein across mucus barriers observed here might be a critical step in the infection of the gastrointestinal epithelium and the development of Parkinson's disease.

Original languageEnglish
Pages (from-to)4332-4344
Number of pages13
JournalBiomacromolecules
Volume20
Issue number12
DOIs
Publication statusPublished - 9 Dec 2019

Keywords

  • UT-Hybrid-D

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