{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T07:33:03Z","timestamp":1792481583502,"version":"4.5.0"},"reference-count":80,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018231","name":"Aligning Science Across Parkinson\u2019s","doi-asserted-by":"publisher","award":["ASAP-020505"],"award-info":[{"award-number":["ASAP-020505"]}],"id":[{"id":"10.13039\/100018231","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson\u2019s Research","doi-asserted-by":"publisher","award":["PID2020-120308RB-I00"],"award-info":[{"award-number":["PID2020-120308RB-I00"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CiberNed Intramural Collaborative Projects","award":["PI2020\/09"],"award-info":[{"award-number":["PI2020\/09"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although neuromelanin is a dark pigment characteristic of dopaminergic neurons in the human substantia nigra pars compacta, its potential role in the pathogenesis of Parkinson\u2019s disease (PD) has often been neglected since most commonly used laboratory animals lack neuromelanin. Here we took advantage of adeno-associated viral vectors encoding the human tyrosinase gene for triggering a time-dependent neuromelanin accumulation within substantia nigra pars compacta dopaminergic neurons in macaques up to similar levels of pigmentation as observed in elderly humans. Furthermore, neuromelanin accumulation induced an endogenous synucleinopathy mimicking intracellular inclusions typically observed in PD together with a progressive degeneration of neuromelanin-expressing dopaminergic neurons.<\/jats:p>\n                  <jats:p>Moreover, Lewy body-like intracellular inclusions were observed in cortical areas of the frontal lobe receiving dopaminergic innervation, supporting a circuit-specific anterograde spread of endogenous synucleinopathy by permissive trans-synaptic templating.<\/jats:p>\n                  <jats:p>In summary, the conducted strategy resulted in the development and characterization of a new macaque model of PD matching the known neuropathology of this disorder with unprecedented accuracy. Most importantly, evidence is provided showing that intracellular aggregation of endogenous \u03b1-synuclein is triggered by neuromelanin accumulation, therefore any therapeutic approach intended to decrease neuromelanin levels may provide appealing choices for the successful implementation of novel PD therapeutics.<\/jats:p>","DOI":"10.1093\/brain\/awad331","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T18:37:55Z","timestamp":1695926275000},"page":"5000-5014","source":"Crossref","is-referenced-by-count":35,"title":["Neuromelanin accumulation drives endogenous synucleinopathy in non-human primates"],"prefix":"10.1093","volume":"146","author":[{"given":"Julia","family":"Chocarro","sequence":"first","affiliation":[{"name":"CNS Gene Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra , 31008 Pamplona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Aligning Science Across Parkinsons\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto J","family":"Rico","sequence":"additional","affiliation":[{"name":"CNS Gene Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra , 31008 Pamplona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Aligning Science Across Parkinsons\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goiaz","family":"Ariznabarreta","sequence":"additional","affiliation":[{"name":"CNS Gene Therapy Program, Center for Applied Medical Research (CIMA), University of Navarra , 31008 Pamplona , Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en 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Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Aligning Science Across Parkinsons\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Collantes","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging Unit, Department of Nuclear Medicine, Cl\u00ednica Universidad de Navarra , 31008 Pamplona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Pe\u00f1uelas","sequence":"additional","affiliation":[{"name":"Translational Molecular Imaging Unit, Department of Nuclear Medicine, Cl\u00ednica Universidad de Navarra , 31008 Pamplona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital Universitario de Navarra, Servicio Navarro de Salud , 31008 Pamplona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana I","family":"Rodr\u00edguez-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Research Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela , 15782 Santiago de Compostela , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8243-9791","authenticated-orcid":false,"given":"Jos\u00e9 L","family":"Labandeira-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Research Center for Molecular Medicine and Chronic Diseases (CIMUS), University of Santiago de Compostela , 15782 Santiago de Compostela , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7376-7470","authenticated-orcid":false,"given":"Miquel","family":"Vila","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (Ciberned-ISCIII) , 28031 Madrid , Spain"},{"name":"Aligning Science Across Parkinsons\u2019s (ASAP) Collaborative Research Network , Chevy Chase, MD 20815 , USA"},{"name":"Vall d\u2019Hebron Research Institute, Neurodegenerative Diseses Research Group , 08035 Barcelona , Spain"},{"name":"Autonomous University of Barcelona (UAB) , 08193 Bellaterra, Barcelona , Spain"},{"name":"Catalan Institution for Research and Advanced Studies (ICREA) , 08010 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2301-5419","authenticated-orcid":false,"given":"Jos\u00e9 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