Identification of distinct pathological signatures induced by patient-derived α-synuclein structures in nonhuman primates
Bourdenx, M. (CNRS)
Nioche, A. (Institut Jean Nicod, Département d'études cognitives, CNRS)
Dovero, S. (CNRS, Institut des Maladies Neurodégénératives)
Arotcarena, M.-L. (CNRS, Institut des Maladies Neurodégénératives)
Camus, S. (CNRS, Institut des Maladies Neurodégénératives)
Porras, G. (CNRS, Institut des Maladies Neurodégénératives)
Thiolat, M.-L. (CNRS, Institut des Maladies Neurodégénératives)
Rougier, N. P. (INRIA Bordeaux Sud-Ouest)
Prigent, A. (CHU Nantes, Department of Neurology, Nantes)
Aubert, P. (CHU Nantes, Department of Neurology)
Bohic, S. (EA-7442 Rayonnement Synchrotron et Recherche Medicale, RSRM, University of Grenoble Alpes)
Sandt, C. (SMIS beamline, Synchrotron SOLEIL, l'orme des merisiers)
Laferrière, F. (CNRS, Institut des Maladies Neurodégénératives)
Doudnikoff, E. (CNRS, Institut des Maladies Neurodégénératives)
Kruse, Niels (University Medical Center Goettingen, Institute of Neuropathology)
Mollenhauer, B. (University Medical Center Goettingen, Institute of Neuropathology)
Novello, Salvatore (University of Ferrara. Neuroscience Center)
Morari, M. (University of Ferrara. Neuroscience Center)
Leste-Lasserre, T. (INSERM, Neurocentre Magendie, U1215, Physiopathologie de la Plasticité Neuronale)
Trigo-Damas, I. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Goillandeau, M. (CNRS, Institut des Maladies Neurodégénératives)
Perier, Celine (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Estrada, C. (Institute of Research on Aging (IUIE), Universidad de Murcia)
Garcia-Carrillo, N. (Centro Experimental en Investigaciones Biomédica (CEIB), Universidad de Murcia)
Recasens, A. (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Vaikath, N. N. (Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar)
El-Agnaf, O. M. A. (Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Education City, Qatar)
Herrero Ezquerdo, María Trinidad (Universidad de Murcia)
Derkinderen, Pascal (CHU Nantes, Department of Neurology)
Vila Bover, Miquel (Institució Catalana de Recerca i Estudis Avançats)
Obeso, J. A. (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)
Dehay, B. (CNRS, Institut des Maladies Neurodégénératives)
Bezard, E. (CNRS, Institut des Maladies Neurodégénératives)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	Machine learning-based approach unravels distinct pathological signatures induced by patient-derived α-synuclein seeds in monkeys. 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.
Ajuts:	Ministerio de Economía y Competitividad SAF2015-67239-P
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Science advances, Vol. 6 (may 2020) , ISSN 2375-2548

DOI: 10.1126/sciadv.aaz9165
PMID: 32426502

18 p, 8.5 MB

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