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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.

We have produced a monoclonal antibody (PM43) selectively reactive with formalin-fixed paraffin-embedded peripheral nervous system (PNS) myelin. The hybridomas were generated by fusion of mouse myeloma cell line Sp2/0 with spleen cells of BALB/c mice immunized with cultured human melanocytes. Hybridomas were screened by the indirect immunoperoxidase assay. Ouchterlony analysis showed the immunoclass of PM43 to be IgM. By the immunoaffinity chromatography technique, among others a 43-kDa protein was isolated from PNS myelin. The antigenic determinant of PM43 in the mouse is expressed with a similar tissue distribution as observed in man. Expression of the antigenic determinant does not become visible until after birth in mice. PM43 opens further possibilities for the use of anti-myelin antibodies in the study of myelination and demyelination processes in the PNS and remyelination processes in the central nervous system.