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Daniel Otzen

Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild-type rats

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  • Line Friis Bakmann Christensen
  • ,
  • Saeid Hadi Alijanvand, Molecular Biology and Genetics Department, Aarhus University, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Tehran, Iran. Electronic address: moosavi@ut.ac.ir., Univ Tehran, Tarbiat Modares University, University of Tehran, Sch Chem Engn, Coll Engn, Catalysis & Nanostruct Mat Res Lab
  • ,
  • Michał Burdukiewicz, Polish Acad Sci, Polish Academy of Sciences, Institute of Nuclear Physics - Polish Academy of Sciences, Henryk Niewodniczanski Inst Nucl Phys
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  • Florian-Alexander Herbst, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
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  • Henrik Kjeldal, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
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  • Morten Simonsen Dueholm, Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg Psychiatric University Hospital, Aalborg, Denmark Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
  • ,
  • Daniel E Otzen

Cross-seeding between amyloidogenic proteins in the gut is receiving increasing attention as a possible mechanism for initiation or acceleration of amyloid formation by aggregation-prone proteins such as αSN, which is central in the development of Parkinson's disease. This is particularly pertinent in view of the growing number of functional (i.e. benign and useful) amyloid proteins discovered in bacteria. Here we identify two amyloidogenic proteins, Pr12 and Pr17, in fecal matter from Parkinson's disease transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid. Both proteins show robust aggregation into ThT-positive aggregates that contain higher-order β-sheets and have a fibrillar morphology, indicative of amyloid proteins. In addition, Pr17 aggregates formed in vitro showed significant resistance against formic acid, suggesting an ability to form highly stable amyloid. Treatment with proteinase K revealed a protected core of approx. 9 kDa. Neither Pr12 nor Pr17, however, affected αSN aggregation in vitro. Thus, amyloidogenicity does not per se lead to an ability to cross-seed fibrillation of αSN. Our results support the use of proteomics and formic acid to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalProtein Science
ISSN0961-8368
DOIs
Publication statusE-pub ahead of print - 1 Jun 2021

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