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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
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  • Saeid Hadi Alijanvand, Univ Tehran, Tarbiat Modares University, University of Tehran, Sch Chem Engn, Coll Engn, Catalysis & Nanostruct Mat Res Lab
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  • 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 Universitet
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  • Henrik Kjeldal, Aalborg Universitet
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  • Morten Simonsen Dueholm, Aalborg Universitet
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  • 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 (PD). 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 PD transgenic rats and their wild type counterparts, based on their stability against dissolution by formic acid (FA). 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 FA, 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 FA to identify amyloidogenic protein in complex mixtures and suggests that there may be numerous functional amyloid proteins in microbiomes.

TidsskriftProtein Science
Sider (fra-til)1854-1870
StatusUdgivet - sep. 2021

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