{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:03:23Z","timestamp":1791288203908,"version":"4.3.0"},"reference-count":28,"publisher":"Rockefeller University Press","issue":"1","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2012,1,16]]},"abstract":"<jats:p>Parkinson\u2019s disease (PD) is a neurodegenerative disorder that results in the loss of nigrostriatal dopamine neurons. The etiology of this cell loss is unknown, but it involves abnormalities in mitochondrial function. In this study, we have demonstrated that the administration of a novel noncoding p137 RNA, derived from the human cytomegaloviral \u03b22.7 transcript, can prevent and rescue dopaminergic cell death in vitro and in animal models of PD by protecting mitochondrial Complex I activity. Furthermore, as this p137 RNA is fused to a rabies virus glycoprotein peptide that facilitates delivery of RNA across the blood\u2013brain barrier, such protection can be achieved through a peripheral intravenous administration of this agent after the initiation of a dopaminergic lesion. This approach has major implications for the potential treatment of PD, especially given that this novel agent could have the same protective effect on all diseased neurons affected as part of this disease process, not just the dopaminergic nigrostriatal pathway.<\/jats:p>","DOI":"10.1084\/jem.20111126","type":"journal-article","created":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T22:41:19Z","timestamp":1324334479000},"page":"1-10","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":36,"title":["A novel neuroprotective therapy for Parkinson\u2019s disease using a viral noncoding RNA that protects mitochondrial Complex I activity"],"prefix":"10.1084","volume":"209","author":[{"given":"Wei-Li","family":"Kuan","sequence":"first","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"},{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Poole","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Karniely","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pam","family":"Tyers","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"},{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Wills","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger A.","family":"Barker","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"},{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Department of Neurology 1 , 2 , 3 ; and 4"},{"name":"Cambridge Centre for Brain Repair 1 , 2 , 3 ; and 4"},{"name":"Department of Medicine, Addenbrooke\u2019s Hospital 1 , 2 , 3 ; and 4"},{"name":"Cancer Research UK Cambridge Research Institute; University of Cambridge, Cambridge CB2 1TN, England, UK 1 , 2 , 3 ; and 4"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2011,12,19]]},"reference":[{"key":"2023072600505925200_bib1","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1038\/nbt.1807","article-title":"Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes","volume":"29","author":"Alvarez-Erviti","year":"2011","journal-title":"Nat. Biotechnol."},{"key":"2023072600505925200_bib2","doi-asserted-by":"crossref","first-page":"8425","DOI":"10.1128\/JVI.72.10.8425-8429.1998","article-title":"The major open reading frame of the beta2.7 transcript of human cytomegalovirus: in vitro expression of a protein posttranscriptionally regulated by the 5\u2032 region","volume":"72","author":"Bergamini","year":"1998","journal-title":"J. Virol."},{"key":"2023072600505925200_bib3","doi-asserted-by":"publisher","first-page":"1301","DOI":"10.1038\/81834","article-title":"Chronic systemic pesticide exposure reproduces features of Parkinson\u2019s disease","volume":"3","author":"Betarbet","year":"2000","journal-title":"Nat. Neurosci."},{"key":"2023072600505925200_bib4","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1111\/j.1460-9568.2006.05285.x","article-title":"Time-course of nigrostriatal damage, basal ganglia metabolic changes and behavioural alterations following intrastriatal injection of 6-hydroxydopamine in the rat: new clues from an old model","volume":"25","author":"Blandini","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"2023072600505925200_bib5","doi-asserted-by":"publisher","first-page":"2042","DOI":"10.1002\/mds.21065","article-title":"Stanley Fahn Lecture 2005: The staging procedure for the inclusion body pathology associated with sporadic Parkinson\u2019s disease reconsidered","volume":"21","author":"Braak","year":"2006","journal-title":"Mov. Disord."},{"key":"2023072600505925200_bib6","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1096\/fj.00-0129com","article-title":"Melatonin protects against 6-OHDA-induced neurotoxicity in rats: a role for mitochondrial complex I activity","volume":"15","author":"Dabbeni-Sala","year":"2001","journal-title":"FASEB J."},{"key":"2023072600505925200_bib7","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/nbt.1560","article-title":"Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors","volume":"27","author":"Dassie","year":"2009","journal-title":"Nat. Biotechnol."},{"key":"2023072600505925200_bib8","doi-asserted-by":"publisher","first-page":"646","DOI":"10.1016\/j.neuron.2010.04.034","article-title":"Genetic animal models of Parkinson\u2019s disease","volume":"66","author":"Dawson","year":"2010","journal-title":"Neuron."},{"key":"2023072600505925200_bib9","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1056\/NEJM200103083441002","article-title":"Transplantation of embryonic dopamine neurons for severe Parkinson\u2019s disease","volume":"344","author":"Freed","year":"2001","journal-title":"N. Engl. J. Med."},{"key":"2023072600505925200_bib10","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1038\/nm850","article-title":"Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease","volume":"9","author":"Gill","year":"2003","journal-title":"Nat. Med."},{"key":"2023072600505925200_bib11","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1128\/jvi.67.1.530-542.1993","article-title":"Evidence from the anti-idiotypic network that the acetylcholine receptor is a rabies virus receptor","volume":"67","author":"Hanham","year":"1993","journal-title":"J. Virol."},{"key":"2023072600505925200_bib12","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1006\/exnr.1998.6848","article-title":"Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hydroxydopamine in the rat","volume":"152","author":"Kirik","year":"1998","journal-title":"Exp. Neurol."},{"key":"2023072600505925200_bib13","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1111\/j.1399-3089.2006.00291.x","article-title":"Increased capacity for axonal outgrowth using xenogenic tissue in vitro and in a rodent model of Parkinson\u2019s disease","volume":"13","author":"Kuan","year":"2006","journal-title":"Xenotransplantation."},{"key":"2023072600505925200_bib14","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1016\/j.nbd.2006.11.001","article-title":"The importance of A9 dopaminergic neurons in mediating the functional benefits of fetal ventral mesencephalon transplants and levodopa-induced dyskinesias","volume":"25","author":"Kuan","year":"2007","journal-title":"Neurobiol. Dis."},{"key":"2023072600505925200_bib15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1038\/nature05901","article-title":"Transvascular delivery of small interfering RNA to the central nervous system","volume":"448","author":"Kumar","year":"2007","journal-title":"Nature."},{"key":"2023072600505925200_bib16","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1002\/ana.20737","article-title":"Randomized controlled trial of intraputamenal glial cell line-derived neurotrophic factor infusion in Parkinson disease","volume":"59","author":"Lang","year":"2006","journal-title":"Ann. Neurol."},{"key":"2023072600505925200_bib17","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1126\/science.1074549","article-title":"Subthalamic GAD gene therapy in a Parkinson\u2019s disease rat model","volume":"298","author":"Luo","year":"2002","journal-title":"Science."},{"key":"2023072600505925200_bib18","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1038\/nbt1122","article-title":"Potent and persistent in vivo anti-HBV activity of chemically modified siRNAs","volume":"23","author":"Morrissey","year":"2005","journal-title":"Nat. Biotechnol."},{"key":"2023072600505925200_bib19","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1212\/WNL.60.1.69","article-title":"Randomized, double-blind trial of glial cell line-derived neurotrophic factor (GDNF) in PD","volume":"60","author":"Nutt","year":"2003","journal-title":"Neurology."},{"key":"2023072600505925200_bib20","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/ana.10720","article-title":"A double-blind controlled trial of bilateral fetal nigral transplantation in Parkinson\u2019s disease","volume":"54","author":"Olanow","year":"2003","journal-title":"Ann. Neurol."},{"key":"2023072600505925200_bib21","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1126\/science.1143780","article-title":"Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson\u2019s disease","volume":"317","author":"Outeiro","year":"2007","journal-title":"Science."},{"key":"2023072600505925200_bib22","article-title":"The Rat Brain: In Stereotaxic Coordinates","author":"Paxinos","year":"1986","edition":"Second edition"},{"key":"2023072600505925200_bib23","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1126\/science.1142984","article-title":"Complex I binding by a virally encoded RNA regulates mitochondria-induced cell death","volume":"316","author":"Reeves","year":"2007","journal-title":"Science."},{"key":"2023072600505925200_bib24","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/S0140-6736(06)68970-8","article-title":"Mitochondrial disease","volume":"368","author":"Schapira","year":"2006","journal-title":"Lancet."},{"key":"2023072600505925200_bib25","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1111\/j.1471-4159.1990.tb02325.x","article-title":"Mitochondrial complex I deficiency in Parkinson\u2019s disease","volume":"54","author":"Schapira","year":"1990","journal-title":"J. Neurochem."},{"key":"2023072600505925200_bib26","doi-asserted-by":"crossref","first-page":"10756","DOI":"10.1523\/JNEUROSCI.23-34-10756.2003","article-title":"Mechanism of toxicity in rotenone models of Parkinson\u2019s disease","volume":"23","author":"Sherer","year":"2003","journal-title":"J. Neurosci."},{"key":"2023072600505925200_bib27","doi-asserted-by":"publisher","first-page":"1541","DOI":"10.1001\/archneur.59.10.1541","article-title":"Effects of coenzyme Q10 in early Parkinson disease: Evidence of slowing of the functional decline","volume":"59","author":"Shults","year":"2002","journal-title":"Arch. Neurol."},{"key":"2023072600505925200_bib28","first-page":"385","article-title":"Assay of mitochondrial functions by resazurin in vitro","volume":"25","author":"Zhang","year":"2004","journal-title":"Acta Pharmacol. Sin."}],"container-title":["Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/1\/1\/1743368\/jem_20111126.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/209\/1\/1\/1743368\/jem_20111126.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T20:51:33Z","timestamp":1690318293000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/209\/1\/1\/40974\/A-novel-neuroprotective-therapy-for-Parkinson-s"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,12,19]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2012,1,16]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20111126","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.13414996.14789106","asserted-by":"object"}]},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2011,12,19]]}}}