. Exposure to the Functional Bacterial Amyloid Protein Curli Enhances Alpha-Synuclein Aggregation in Aged Fischer 344 Rats and Caenorhabditis elegans. Sci Rep. 2016 Oct 6;6:34477. PubMed.


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  1. The study by Chen et al. offers a possible explanation as to how Parkinson’s disease (PD)-related pathology may appear in the gut and subsequently spread to the CNS. By using two different animal models, rats and nematodes, the authors found that the presence of a certain E.coli strain that produces an amyloidogenic protein, curli, seems to trigger aggregation of α-synuclein, the protein forming amyloid aggregates in the PD brain.

    This investigation builds on the observation that Parkinson’s patients frequently display deposition of α-synuclein in the colon mucosa (Braak et al., 2006) and that rats that had been injected with α-synuclein in the gut wall were found to develop pathology in the dorsal motor nucleus of the vagus nerve (Holmqvist et al., 2014). 

    Seeding and cross-seeding between proteins with amyloidogenic properties have been previously described. For example, certain forms of both amyloid-β and α-synuclein can both seed themselves and cross-seed each other (Ono et al., 2012). As for bacterial amyloids, they have also been suggested to have cross-seeding properties. For example, curli fibrils have been shown to cross-seed serum amyloid A (Lundmark et al., 2005), a protein with an amphipathic helical structure similar to α-synuclein.

    Taken together, the current study and previous observations indicate that specific tertiary structures can make certain proteins capable of inducing formation of pathogenic amyloids. The possibility of such cross-seeding events in the gut, resulting in the formation and subsequent transport of α-synuclein aggregates to the Parkinson’s brain, may offer a novel target for prevention and/or pharmacological treatment. However, additional studies are needed to understand these molecular interactions, including the more exact nature of the propagating α-synuclein species.


    . Gastric alpha-synuclein immunoreactive inclusions in Meissner's and Auerbach's plexuses in cases staged for Parkinson's disease-related brain pathology. Neurosci Lett. 2006 Mar 20;396(1):67-72. PubMed.

    . Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats. Acta Neuropathol. 2014 Dec;128(6):805-20. Epub 2014 Oct 9 PubMed.

    . Cross-seeding effects of amyloid β-protein and α-synuclein. J Neurochem. 2012 Sep;122(5):883-90. PubMed.

    . Protein fibrils in nature can enhance amyloid protein A amyloidosis in mice: Cross-seeding as a disease mechanism. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6098-102. PubMed.

    View all comments by Joakim Bergstrom
  2. I thought the paper was interesting, potentially the first example of cross-seeding that would provide an explanation for at least some cases of idiopathic disease. The outstanding issue is whether it is actually cross-seeding, or if the curli protein interferes with protein degradation promoting persistence of misfolded proteins generally. Some type of in vitro conversion experiment would help answer this.

    View all comments by Robert Petersen

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