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.
journal_name
Biomacromoleculesjournal_title
Biomacromoleculesauthors
Marczynski M,Rickert CA,Semerdzhiev SA,van Dijk WR,Segers-Nolten IMJ,Claessens MMAE,Lieleg Odoi
10.1021/acs.biomac.9b00905subject
Has Abstractpub_date
2019-12-09 00:00:00pages
4332-4344issue
12eissn
1525-7797issn
1526-4602journal_volume
20pub_type
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