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

15 Citations (Scopus)
58 Downloads (Pure)

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
  • 22/4 OA procedure

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