BOURDENX, Mathieu; NIOCHE, Aurelien; DOVERO, Sandra; AROTCARENA, Marie Laure; CAMUS, Sandrine; PORRAS, Gregory; THIOLAT, Marie-Laure; ROUGIER, Nicolas; PRIGENT, Alice; AUBERT, Philippe; BOHIC, Sylvain; SANDT, Christophe; LAFERRIERE, Florent; DOUDNIKOFF, Evelyne; KRUSE, Niels; MOLLENHAUER, Brit; NOVELLO, Salvatore; MORARI, Michele; LESTE-LASSERRE, Thierry; TRIGO DAMAS, Ines; GOILLANDEAU, Michel; PERIER, Celine; ESTRADA, Cristina; GARCIA-CARRILLO, Nuria; RECASENS, Ariadna; VAIKATH, Nishant Narayanan; EL-AGNAF, Omar; HERRERO, Maria Trinidad; DERKINDEREN, Pascal; VILA, Miquel; OBESO, Jose A; DEHAY, Benjamin; BEZARD, Erwan

doi:10.1126/sciadv.aaz9165

Institut des Maladies Neurodégénératives [Bordeaux] [IMN]

NIOCHE, Aurelien
Institut des Maladies Neurodégénératives [Bordeaux] [IMN]

DOVERO, Sandra
Institut des Maladies Neurodégénératives [Bordeaux] [IMN]

Langue

Article de revue

Ce document a été publié dans

Science Advances. 2020-05-13, vol. 6, n° 20

Résumé en anglais

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. © 2020 American Association for the Advancement of Science. All rights reserved.< Réduire

Mots clés en anglais

Aggregates

Cell Death

Amyloid Fibril

Disease Progression

Experimental Models

Neurodegeneration

Neuronal Cell

Non-Human Primate

Parkinson's Disease

Protein Aggregates

Mammals

Alpha Synuclein

Amyloid

Animal

Chemistry

Human

Lewy Body

Metabolism

Pathology

Primate

Animals

Humans

Lewy Bodies

Primates

URI

https://oskar-bordeaux.fr/handle/20.500.12278/184631

DOI

http://dx.doi.org/10.1126/sciadv.aaz9165

Project ANR

Développment d'une infrastructure française distribuée coordonnée - ANR-10-INBS-0004
Bordeaux Region Aquitaine Initiative for Neuroscience - ANR-10-LABX-0043

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

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Mots clés en anglais

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

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Ce document a été publié dans

Résumé en anglais

Mots clés en anglais

URI

DOI

Project ANR

Unités de recherche