{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:52:17Z","timestamp":1790614337136,"version":"4.1.0"},"reference-count":47,"publisher":"Society for Neuroscience","issue":"17","license":[{"start":{"date-parts":[[2017,10,26]],"date-time":"2017-10-26T00:00:00Z","timestamp":1508976000000},"content-version":"vor","delay-in-days":209,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2017,4,26]]},"abstract":"<jats:p>Transforming growth factor-\u03b2 (TGF-\u03b2) plays an important role in the development and maintenance of embryonic dopaminergic (DA) neurons in the midbrain. To study the function of TGF-\u03b2 signaling in the adult nigrostriatal system, we generated transgenic mice with reduced TGF-\u03b2 signaling in mature neurons. These mice display age-related motor deficits and degeneration of the nigrostriatal system. Increasing TGF-\u03b2 signaling in the substantia nigra through adeno-associated virus expressing a constitutively active type I receptor significantly reduces 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration and motor deficits. These results suggest that TGF-\u03b2 signaling is critical for adult DA neuron survival and that modulating this signaling pathway has therapeutic potential in Parkinson disease.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>\n                    We show that reducing Transforming growth factor-\u03b2 (TGF-\u03b2) signaling promotes Parkinson disease-related pathologies and motor deficits, and increasing TGF-\u03b2 signaling reduces neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, a parkinsonism-inducing agent. Our results provide a rationale to pursue a means of increasing TGF-\u03b2 signaling as a potential therapy for Parkinson's disease.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2952-16.2017","type":"journal-article","created":{"date-parts":[[2017,3,31]],"date-time":"2017-03-31T21:00:18Z","timestamp":1490994018000},"page":"4584-4592","source":"Crossref","is-referenced-by-count":83,"title":["Deficiency in Neuronal TGF-\u03b2 Signaling Leads to Nigrostriatal Degeneration and Activation of TGF-\u03b2 Signaling Protects against MPTP Neurotoxicity in Mice"],"prefix":"10.1523","volume":"37","author":[{"given":"Ina","family":"Tesseur","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betty","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0298-3800","authenticated-orcid":false,"given":"Nathaniel S.","family":"Woodling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tony","family":"Wyss-Coray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-8467","authenticated-orcid":false,"given":"Jian","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2017,3,31]]},"reference":[{"key":"2023041803245030000_37.17.4584.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.09.001"},{"key":"2023041803245030000_37.17.4584.2","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20425"},{"key":"2023041803245030000_37.17.4584.3","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.281"},{"key":"2023041803245030000_37.17.4584.4","doi-asserted-by":"publisher","DOI":"10.1006\/exnr.2000.7409"},{"key":"2023041803245030000_37.17.4584.5","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/16.10.2621"},{"key":"2023041803245030000_37.17.4584.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2652"},{"key":"2023041803245030000_37.17.4584.7","doi-asserted-by":"crossref","first-page":"8778","DOI":"10.1523\/JNEUROSCI.17-22-08778.1997","article-title":"Targeted overexpression of the neurite growth-associated protein B-50\/GAP-43 in cerebellar Purkinje cells induces sprouting after axotomy but not axon regeneration into growth-permissive transplants","volume":"17","author":"Buffo","year":"1997","journal-title":"J Neurosci"},{"key":"2023041803245030000_37.17.4584.8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2980-05.2005"},{"key":"2023041803245030000_37.17.4584.9","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90207-0"},{"key":"2023041803245030000_37.17.4584.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"2023041803245030000_37.17.4584.11","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1523\/JNEUROSCI.21-03-00788.2001","article-title":"DNA hypomethylation perturbs the function and survival of CNS neurons in postnatal animals","volume":"21","author":"Fan","year":"2001","journal-title":"J Neurosci"},{"key":"2023041803245030000_37.17.4584.12","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-006-0414-6"},{"key":"2023041803245030000_37.17.4584.13","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00254-08"},{"key":"2023041803245030000_37.17.4584.14","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8639-3"},{"key":"2023041803245030000_37.17.4584.15","doi-asserted-by":"publisher","DOI":"10.1017\/erm.2015.6"},{"key":"2023041803245030000_37.17.4584.16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4506-03.2004"},{"key":"2023041803245030000_37.17.4584.17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1422448112"},{"key":"2023041803245030000_37.17.4584.18","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3742"},{"key":"2023041803245030000_37.17.4584.19","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(94)90583-5"},{"key":"2023041803245030000_37.17.4584.20","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/j.1460-2075.1995.tb07052.x","article-title":"TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity","volume":"14","author":"Krieglstein","year":"1995","journal-title":"EMBO J"},{"key":"2023041803245030000_37.17.4584.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0605077103"},{"key":"2023041803245030000_37.17.4584.22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31763"},{"key":"2023041803245030000_37.17.4584.23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20120412"},{"key":"2023041803245030000_37.17.4584.24","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2014.00012"},{"key":"2023041803245030000_37.17.4584.25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI63113"},{"key":"2023041803245030000_37.17.4584.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5293.1678"},{"key":"2023041803245030000_37.17.4584.27","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-2011-11023"},{"key":"2023041803245030000_37.17.4584.28","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(95)11686-Q"},{"key":"2023041803245030000_37.17.4584.29","first-page":"435","article-title":"A simple quantitative bradykinesia test in MPTP-treated mice","volume":"50","author":"Ogawa","year":"1985","journal-title":"Res Commun Chem Pathol Pharmacol"},{"key":"2023041803245030000_37.17.4584.30","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(94)90062-0"},{"key":"2023041803245030000_37.17.4584.31","doi-asserted-by":"publisher","DOI":"10.1126\/science.1141736"},{"key":"2023041803245030000_37.17.4584.32","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90049-6"},{"key":"2023041803245030000_37.17.4584.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.025"},{"key":"2023041803245030000_37.17.4584.34","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.2005-0514"},{"key":"2023041803245030000_37.17.4584.35","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-0322-8_8"},{"key":"2023041803245030000_37.17.4584.36","doi-asserted-by":"publisher","DOI":"10.1126\/science.3131879"},{"key":"2023041803245030000_37.17.4584.37","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-virology-031413-085355"},{"key":"2023041803245030000_37.17.4584.38","doi-asserted-by":"publisher","DOI":"10.1016\/S1044-7431(03)00081-2"},{"key":"2023041803245030000_37.17.4584.39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.19.8935"},{"key":"2023041803245030000_37.17.4584.40","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-6-72"},{"key":"2023041803245030000_37.17.4584.41","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27341"},{"key":"2023041803245030000_37.17.4584.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.12.018"},{"key":"2023041803245030000_37.17.4584.43","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3569"},{"key":"2023041803245030000_37.17.4584.44","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2386"},{"key":"2023041803245030000_37.17.4584.45","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1002\/j.1460-2075.1995.tb07214.x","article-title":"GS domain mutations that constitutively activate T beta R-I, the downstream signaling component in the TGF-beta receptor complex","volume":"14","author":"Wieser","year":"1995","journal-title":"EMBO J"},{"key":"2023041803245030000_37.17.4584.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.12.036"},{"key":"2023041803245030000_37.17.4584.47","doi-asserted-by":"publisher","DOI":"10.1038\/nn1816"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2952-16.2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,18]],"date-time":"2023-04-18T06:58:25Z","timestamp":1681801105000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2952-16.2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,3,31]]},"references-count":47,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2017,4,26]]},"published-print":{"date-parts":[[2017,4,26]]}},"alternative-id":["10.1523\/JNEUROSCI.2952-16.2017"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2952-16.2017","relation":{},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,3,31]]}}}