α-Synuclein penetrates mucin hydrogels despite its mucoadhesive properties.

α-Synuclein penetrates mucin hydrogels despite its mucoadhesive properties. Biomacromolecules. 2019 Nov 13;: Authors: Marczynski M, Rickert CA, Semerdzhiev SA, van Dijk WR, Segers-Nolten IMJ, Claessens MMAE, Lieleg O 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 non-infected 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. PMID: 31721560 [PubMed - as supplied by publisher]
Source: Biomacromolecules - Category: Biochemistry Authors: Tags: Biomacromolecules Source Type: research