{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:47:32Z","timestamp":1776235652836,"version":"3.50.1"},"reference-count":45,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2014,6,16]],"date-time":"2014-06-16T00:00:00Z","timestamp":1402876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Chinese National 973 Projects Grant","award":["2011CB510000"],"award-info":[{"award-number":["2011CB510000"]}]},{"name":"FMMU Research Foundation"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31371400"],"award-info":[{"award-number":["31371400"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Progressive loss of dopaminergic (DA) neurons in the substantial nigra pars compacta (SNc) is an important pathological feature in Parkinson's disease (PD). Loss of transcription factor myocyte enhancer factor 2D (MEF2D), a key neuronal survival factor, has been shown to underlie the loss of DA neurons in SNc and the pathogenic process of PD. It is known that PD\u2010associated neurotoxins reduce the level of MEF2D protein to trigger neuronal death. Although neurotoxins clearly destabilize MEF2D by post\u2010translational mechanisms, it is not known whether regulation of MEF2D <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> contributes to neurotoxin\u2010induced decrease in MEF2D protein. In this work, we showed that MPP<jats:sup>+<\/jats:sup>, the toxic metabolite of MPTP, caused a significant decrease in the half\u2010life and total level of MEF2D <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in a DA neuronal cell line, SN4741 cells. Quantitative PCR analysis of the SNc DA neurons captured by immune\u2010laser capture microdissection showed that exposure to MPTP led to a marked reduction in the level of MEF2D <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> in SNc DA neurons compared to controls. Down\u2010regulation of MEF2D <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> alone reduced the viability of SN4741 cells and sensitized the cells to MPP<jats:sup>+<\/jats:sup>\u2010induced toxicity. These results suggest that destabilization and reduction in MEF2D <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> is in part responsible for neurotoxin\u2010induced decrease in MEF2D protein and neuronal viability.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12765-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nMyocyte enhancer factor 2D (MEF2D) plays an important role in neuronal survival. How MEF2D mRNA is deregulated under toxic stress is unclear. We found that PD\u2010associated neurotoxins destabilize MEF2D mRNA and reduce its level <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>. Reduction in MEF2D mRNA is sufficient to sensitize model cells to neurotoxin\u2010induced toxicity, suggesting that destabilization of MEF2D mRNA is part of the mechanism by which neurotoxins trigger deregulation of neuronal survival.<\/jats:p>","DOI":"10.1111\/jnc.12765","type":"journal-article","created":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T08:55:28Z","timestamp":1400748928000},"page":"720-728","source":"Crossref","is-referenced-by-count":29,"title":["Destabilization of survival factor MEF2D <scp>mRNA<\/scp> by neurotoxin in models of Parkinson's disease"],"prefix":"10.1111","volume":"130","author":[{"given":"Bao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Tangdu Hospital the Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhibiao","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tangdu Hospital the Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangfang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tangdu Hospital the Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Li","sequence":"additional","affiliation":[{"name":"Ningxia Key Laboratory of Cerebrocranial Diseases Ningxia Medical University Yinchuan Ningxia China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaofei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Neurology KunMing General Hospital of The People's Liberation Army Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linna","family":"Su","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Cancer Biology and Institute of Digestive Diseases Xijing Hospital of Digestive Diseases Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guodong","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tangdu Hospital the Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Tangdu Hospital the Fourth Military Medical University Xi'an Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,6,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01128"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.9.6.730"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0290023"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00568-3"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01256"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.4.3.415"},{"key":"e_1_2_7_8_1","doi-asserted-by":"crossref","first-page":"R58","DOI":"10.1186\/bcr1608","article-title":"Gene expression signatures of morphologically normal breast tissue identify basal\u2010like tumors","volume":"8","author":"Finak G.","year":"2006","journal-title":"Breast Cancer Res."},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(03)00191-0"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00350-X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:29:2:155"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.3.4.539"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.342"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(06)70471-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.10.023"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"6544","DOI":"10.1523\/JNEUROSCI.21-17-06544.2001","article-title":"Myocyte enhancer factor 2A and 2D undergo phosphorylation and caspase\u2010mediated degradation during apoptosis of rat cerebellar granule neurons","volume":"21","author":"Li M.","year":"2001","journal-title":"J. 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