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 language | English |
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Pages (from-to) | 4332-4344 |
Number of pages | 13 |
Journal | Biomacromolecules |
Volume | 20 |
Issue number | 12 |
DOIs | |
Publication status | Published - 9 Dec 2019 |
Keywords
- UT-Hybrid-D
- 22/4 OA procedure