α-Synuclein Penetrates Mucin Hydrogels Despite Its Mucoadhesive Properties.

Autor:	Marczynski M; Department of Mechanical Engineering and Munich School of Bioengineering , Technical University of Munich , Garching 85748 , Germany., Rickert CA; Department of Mechanical Engineering and Munich School of Bioengineering , Technical University of Munich , Garching 85748 , Germany., Semerdzhiev SA; Nanobiophysics, Faculty of Science and Technology , University of Twente , Enschede 7522NB , The Netherlands., van Dijk WR; Nanobiophysics, Faculty of Science and Technology , University of Twente , Enschede 7522NB , The Netherlands., Segers-Nolten IMJ; Nanobiophysics, Faculty of Science and Technology , University of Twente , Enschede 7522NB , The Netherlands., Claessens MMAE; Nanobiophysics, Faculty of Science and Technology , University of Twente , Enschede 7522NB , The Netherlands., Lieleg O; Department of Mechanical Engineering and Munich School of Bioengineering , Technical University of Munich , Garching 85748 , Germany.
Jazyk:	angličtina
Zdroj:	Biomacromolecules [Biomacromolecules] 2019 Dec 09; Vol. 20 (12), pp. 4332-4344. Date of Electronic Publication: 2019 Nov 25.
DOI:	10.1021/acs.biomac.9b00905
Abstrakt:	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.
Databáze:	MEDLINE
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