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Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates

DOI: 10.1126/sciadv.aaz9165 DOI Help

Authors: M. Bourdenx (Univ. de Bordeaux; CNRS) , A. Nioche (Univ. de Bordeaux; CNRS; PSL Research University) , S. Dovero (Univ. de Bordeaux; CNRS) , M.-l. Arotcarena (Univ. de Bordeaux; CNRS) , S. Camus (Univ. de Bordeaux; CNRS) , G. Porras (Univ. de Bordeaux; CNRS) , M.-l. Thiolat (Univ. de Bordeaux; CNRS) , N. P. Rougier (Univ. de Bordeaux; CNRS; INRIA Bordeaux Sud-Ouest) , A. Prigent (INSERM; Nantes University; CHU Nantes) , P. Aubert (INSERM; Nantes University; CHU Nantes) , S. Bohic (Rayonnement Synchrotron et Recherche Medicale, RSRM, University of Grenoble Alpes) , C. Sandt (Synchrotron SOLEIL) , F. Laferrière (Univ. de Bordeaux; CNRS) , E. Doudnikoff (Univ. de Bordeaux; CNRS) , N. Kruse (Paracelsus-Elena-Klinik; University Medical Center Goettingen) , B. Mollenhauer (Paracelsus-Elena-Klinik; University Medical Center Goettingen) , S. Novello (University of Ferrara) , M. Morari (University of Ferrara) , T. Leste-lasserre (INSERM) , I. Trigo Damas (HM Puerta del Sur and CEU–San Pablo University Madrid; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III) , M. Goillandeau (Univ. de Bordeaux; CNRS) , C. Perier (Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III) , C. Estrada (University of Murcia) , N. Garcia-carrillo (Universidad de Murcia) , A. Recasens (Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III) , N. N. Vaikath (Hamad Bin Khalifa University (HBKU)) , O. M. A. El-agnaf (Hamad Bin Khalifa University (HBKU)) , M. T. Herrero (University of Murcia) , P. Derkinderen (INSERM; Nantes University; CHU Nantes) , M. Vila (Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III; Autonomous University of Barcelona (UAB); Catalan Institution for Research and Advanced Studies (ICREA)) , J. A. Obeso (HM Puerta del Sur and CEU–San Pablo University Madrid; Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Instituto Carlos III) , B. Dehay (Univ. de Bordeaux; CNRS) , E. Bezard (Univ. de Bordeaux; CNRS)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science Advances , VOL 6

State: Published (Approved)
Published: May 2020
Diamond Proposal Number(s): 13009

Open Access Open Access

Abstract: Dopaminergic neuronal cell death, associated with intracellular α-synuclein (α-syn)–rich protein aggregates [termed “Lewy bodies” (LBs)], is a well-established characteristic of Parkinson’s disease (PD). Much evidence, accumulated from multiple experimental models, has suggested that α-syn plays a role in PD pathogenesis, not only as a trigger of pathology but also as a mediator of disease progression through pathological spreading. Here, we have used a machine learning–based approach to identify unique signatures of neurodegeneration in monkeys induced by distinct α-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular α-syn aggregates is as toxic as larger amyloid fibrils present in the LBs, thus reinforcing the need for preclinical research in this species. Furthermore, our results provide evidence supporting the true multifactorial nature of PD, as multiple causes can induce a similar outcome regarding dopaminergic neurodegeneration.

Subject Areas: Biology and Bio-materials


Instruments: I18-Microfocus Spectroscopy

Documents:
eaaz9165.full.pdf