Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates
Year: 2020
Type: article
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.
Source: Science Advances
Authors: M. Bourdenx, A. Nioche, S. Dovero, M.-L. Arotcarena, S. Camus, G. Porras, M.-L. Thiolat, N. P. Rougier, A. Prigent, P. Aubert, S. Bohic, C. Sandt, F. Laferrière, E. Doudnikoff, N. Kruse, B. Mollenhauer, S. Novello, M. Morari, T. Leste-Lasserre, I. Trigo Damas, M. Goillandeau, C. Perier, C. Estrada, N. Garcia-Carrillo, A. Recasens, N. N. Vaikath, O. M. A. El-Agnaf, M. Trinidad Herrero, P. Derkinderen, M. Vila, J. A. Obeso, B. Dehay, E. Bezard
Institutions: Centre National de la Recherche Scientifique, Université de Bordeaux, Institut des Maladies Neurodégénératives, Université Paris Sciences et Lettres, École Normale Supérieure - PSL, Institut Jean Nicod, École des hautes études en sciences sociales, Institut national de recherche en sciences et technologies du numérique, Centre Inria de l'université de Bordeaux, Inserm, Centre Hospitalier Universitaire de Nantes, Université de Nantes, Nantes Université, Université Grenoble Alpes, Synchrotron SOLEIL, Universitätsmedizin Göttingen, Paracelsus Elena Klinik Kassel, University of Ferrara, Neurocentre Magendie, Universidad San Pablo CEU, Instituto de Salud Carlos III, Biomedical Research Networking Center on Neurodegenerative Diseases, Vall d'Hebron Institut de Recerca, Instituto Murciano de Investigación Biosanitaria, Universidad de Murcia, Hamad bin Khalifa University, Institució Catalana de Recerca i Estudis Avançats, Universitat Autònoma de Barcelona
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,567
Funders: Michael J. Fox Foundation for Parkinson's Research, Fundación Séneca, Ministère de l’Enseignement Supérieur et de la Recherche Scientifique, Agence Nationale de la Recherche, Universidad de Murcia, Ministère de l'Enseignement Supérieur et de la Recherche, Centre National de la Recherche Scientifique, Université de Bordeaux, Association France Parkinson, LabEx BRAIN, Parkinsonfonden, Académie des Sciences, Institut de France
OpenAlex ID: W3025431232