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

被引：41

作者：

Bourdenx, M. ^{[1
,2
,27
]}

Nioche, A. ^{[1
,2
,3
,4
,28
]}

Dovero, S. ^{[1
,2
]}

Arotcarena, M-L ^{[1
,2
]}

Camus, S. ^{[1
,2
]}

Porras, G. ^{[1
,2
]}

Thiolat, M-L ^{[1
,2
]}

Rougier, N. P. ^{[1
,2
,5
]}

Prigent, A. ^{[6
,7
,8
]}

Aubert, P. ^{[6
,7
,8
]}

Bohic, S. ^{[9
]}

Sandt, C. ^{[10
]}

Laferriere, F. ^{[1
,2
]}

Doudnikoff, E. ^{[1
,2
]}

Kruse, N. ^{[11
,12
]}

Mollenhauer, B. ^{[11
,12
]}

Novello, S. ^{[13
,14
,15
]}

Morari, M. ^{[13
,14
,15
]}

Leste-Lasserre, T. ^{[16
]}

Trigo Damas, I ^{[17
,18
,19
]}

Goillandeau, M. ^{[1
,2
]}

Perier, C. ^{[19
,20
]}

Estrada, C. ^{[21
,22
]}

Garcia-Carrillo, N. ^{[23
]}

Recasens, A. ^{[19
,20
]}

Vaikath, N. N. ^{[24
]}

El-Agnaf, O. M. A. ^{[24
]}

Herrero, M. T. ^{[21
,22
]}

Derkinderen, P. ^{[6
,7
,8
]}

Vila, M. ^{[19
,20
,25
,26
]}

Obeso, J. A. ^{[17
,18
,19
]}

Dehay, B. ^{[1
,2
]}

Bezard, E. ^{[1
,2
]}

机构：

[1] Univ Bordeaux, Inst Malad Neurodegeneratives, UMR 5293, F-33000 Bordeaux, France

[2] CNRS, Inst Malad Neurodegeneratives, UMR 5293, F-33000 Bordeaux, France

[3] PSL Res Univ, EHESS, ENS, Inst Jean Nicod,Dept Etud Cognit, F-75005 Paris, France

[4] CNRS, Dept Etud Cognit, Inst Jean Nicod, UMR 8129, Paris, France

[5] INRIA Bordeaux Sud Ouest, F-33405 Talence, France

[6] INSERM, U1235, F-44035 Nantes, France

[7] Nantes Univ, F-44035 Nantes, France

[8] CHU Nantes, Dept Neurol, F-44093 Nantes, France

[9] Univ Grenoble Alpes, RSRM, EA 7442 Rayonnement Synchrotron & Rech Med, F-38000 Grenoble, France

[10] Synchrotron SOLEIL, SMIS Beamline, F-91192 Gif Sur Yvette, France

[11] Paracelsus Elena Klin, Kassel, Germany

[12] Univ Med Ctr Goettingen, Inst Neuropathol, Gottingen, Germany

[13] Univ Ferrara, Dept Med Sci, Sect Pharmacol, Via Fossato Mortara 17-19, I-44121 Ferrara, Italy

[14] Univ Ferrara, Neurosci Ctr, Via Fossato Mortara 17-19, I-44121 Ferrara, Italy

[15] Univ Ferrara, Natl Inst Neurosci, Via Fossato Mortara 17-19, I-44121 Ferrara, Italy

[16] INSERM, Neuroctr Magendie, U1215, Physiopathol Plasticite Neuronale, F-33000 Bordeaux, France

[17] HM Puerta, HM CINAC, E-28938 Mostoles, Spain

[18] San Pablo Univ Madrid, CEU, E-28938 Mostoles, Spain

[19] Inst Carlos III, Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Madrid, Spain

[20] Vall dHebron Res Inst VHIR, Ctr Networked Biomed Res Neurodegenerat Dis CIBER, Neurodegenerat Dis Res Grp, Barcelona, Spain

[21] Univ Murcia, Sch Med, Biomed Res Inst Murcia IMIB, Clin & Expt Neurosci Unit, Campus Mare Nostrum, Murcia 30100, Spain

[22] Univ Murcia, Sch Med, Inst Res Aging IUIE, Murcia 30100, Spain

[23] Univ Murcia, Ctr Expt Invest Biomed CEIB, Murcia, Spain

[24] Hamad Bin Khalifa Univ HBKU, Qatar Biomed Res Inst QBRI, Neurol Disorders Res Ctr, Education City, Qatar

[25] Autonomous Univ Barcelona UAB, Dept Biochem & Mol Biol, Barcelona, Spain

[26] Catalan Inst Res & Adv Studies ICREA, Barcelona, Spain

[27] Albert Einstein Coll Med, Dept Dev & Mol Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[28] Aalto Univ, Sch Elect Engn, Dept Commun & Networking, Espoo 02150, Finland

来源：

SCIENCE ADVANCES | 2020年 / 6卷 / 20期

关键词：

PARKINSONS-DISEASE; NEURONS; NEURODEGENERATION; PUBLICATION; DEFICIENCY; OLIGOMERS;

D O I：

10.1126/sciadv.aaz9165

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dopaminergic neuronal cell death, associated with intracellular alpha-synuclein (alpha-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 alpha-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 alpha-syn pathogenic structures derived from patients with PD. Unexpectedly, our results show that, in nonhuman primates, a small amount of singular alpha-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.

引用

页数：18

共 59 条

[1] Lentiviral Overexpression of GRK6 Alleviates L-Dopa-Induced Dyskinesia in Experimental Parkinson's Disease [J].