{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:32:48Z","timestamp":1791973968558,"version":"4.4.0"},"reference-count":51,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,6,17]],"date-time":"2018-06-17T00:00:00Z","timestamp":1529193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81721005"],"award-info":[{"award-number":["No. 81721005"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81471377"],"award-info":[{"award-number":["No. 81471377"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 81473198"],"award-info":[{"award-number":["No. 81473198"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No.81773712"],"award-info":[{"award-number":["No.81773712"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2019,2]]},"abstract":"Summary<\/jats:title>Aims<\/jats:title>Palmitoylation of \u03b1\u2010amino\u20103\u2010hydroxy\u20105\u2010methyl\u20104\u2010isoxazolepropionic acid receptors (AMPAR<\/jats:styled-content>s) subunits or their \u201cscaffold\u201d proteins produce opposite effects on AMPAR<\/jats:styled-content> surface delivery. Considering AMPAR<\/jats:styled-content>s have long been identified as suitable drug targets for central nervous system (CNS<\/jats:styled-content>) disorders, targeting palmitoylation signaling to regulate AMPAR<\/jats:styled-content> function emerges as a novel therapeutic strategy. However, until now, much less is known about the effect of palmitoylation\u2010deficient state on AMPAR<\/jats:styled-content> function. Herein, we set out to determine the effect of global de\u2010palmitoylation on AMPAR<\/jats:styled-content> surface expression and its function, using a special chemical tool, N\u2010(tert\u2010Butyl) hydroxylamine (NtBuHA<\/jats:styled-content>).<\/jats:p><\/jats:sec>Methods<\/jats:title>BS<\/jats:styled-content>3<\/jats:sup> protein cross\u2010linking, Western blot, immunoprecipitation, patch clamp, and biotin switch assay.<\/jats:p><\/jats:sec>Results<\/jats:title>Bath application of NtBuHA<\/jats:styled-content> (1.0 mM<\/jats:styled-content>) reduced global palmitoylated proteins in the hippocampus of mice. Although NtBuHA<\/jats:styled-content> (1.0 mM<\/jats:styled-content>) did not affect the expression of ionotropic glutamate receptor subunits, it preferentially decreased the surface expression of AMPAR<\/jats:styled-content>s, not N<\/jats:italic>\u2010methyl\u2010d\u2010aspartate receptors (NMDAR<\/jats:styled-content>s). Notably, NtBuHA<\/jats:styled-content> (1.0 mM<\/jats:styled-content>) reduces AMPAR<\/jats:styled-content>\u2010mediated excitatory postsynaptic currents (mEPSC<\/jats:styled-content>s) in the hippocampus. This effect may be largely due to the de\u2010palmitoylation of postsynaptic density protein 95 (PSD<\/jats:styled-content>95) and protein kinase A\u2010anchoring proteins, both of which stabilized AMPAR<\/jats:styled-content> synaptic delivery. Furthermore, we found that changing PSD<\/jats:styled-content>95 palmitoylation by NtBuHA<\/jats:styled-content> altered the association of PSD<\/jats:styled-content>95 with stargazin, which interacted directly with AMPAR<\/jats:styled-content>s, but not NMDARs.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our data suggest that the palmitoylation\u2010deficient state initiated by NtBuHA<\/jats:styled-content> preferentially reduces AMPAR<\/jats:styled-content> function, which may potentially be used for the treatment of CNS<\/jats:styled-content> disorders, especially infantile neuronal ceroid lipofuscinosis (Batten disease).<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12996","type":"journal-article","created":{"date-parts":[[2018,6,18]],"date-time":"2018-06-18T05:10:14Z","timestamp":1529298614000},"page":"187-199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["De\u2010palmitoylation by N\u2010(tert\u2010Butyl) hydroxylamine inhibits AMPAR<\/scp>\u2010mediated synaptic transmission via affecting receptor distribution in postsynaptic densities"],"prefix":"10.1111","volume":"25","author":[{"given":"Zhi\u2010Xuan","family":"Xia","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010Cheng","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao\u2010Qi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai\u2010Lei","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2010Guo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province Wuhan China"},{"name":"Laboratory of Neuropsychiatric Diseases The Institute of Brain Research Huazhong University of Science and Technology Wuhan China"},{"name":"The Collaborative\u2010Innovation Center for Brain Science Wuhan China"},{"name":"The Key Laboratory of Neurological Diseases (HUST) Ministry of Education of China Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province Wuhan China"},{"name":"Laboratory of Neuropsychiatric Diseases The Institute of Brain Research Huazhong University of Science and Technology Wuhan China"},{"name":"The Collaborative\u2010Innovation Center for Brain Science Wuhan China"},{"name":"The Key Laboratory of Neurological Diseases (HUST) Ministry of Education of China Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5042-3381","authenticated-orcid":false,"given":"Peng\u2010Fei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan China"},{"name":"The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province Wuhan China"},{"name":"Laboratory of Neuropsychiatric Diseases The Institute of Brain Research Huazhong University of Science and Technology Wuhan China"},{"name":"The Key Laboratory of Neurological Diseases (HUST) Ministry of Education of China Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.25.112701.142758"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.12.006"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2011.06.008"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20130081"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2788"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2014.12.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(97)80056-7"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.06.035"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2351"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0784-12.2012"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2243-14.2015"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00683-9"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1612963113"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.148.1.159"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-9745-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.08.017"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049089"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R115.652750"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2015.06.004"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9753-0"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02221-9"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3526"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14612"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.11.025"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.2014.874416"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apcsb.2015.10.004"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.1.261"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.005"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.06.039"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0004135"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2004.12.005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb400380s"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.04.015"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12532"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-016-2006-x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2016.6936"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.12585"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2300"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2594-13.2014"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.76"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1952.sp004735"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/0301-0082(91)90019-W"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2005.12.018"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2007.09.012"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2010.10.010"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28685"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0387-17.2018"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.33.21105"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.030"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.7b00959"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-09-03493.2002"}],"container-title":["CNS Neuroscience & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.12996","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.12996","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T04:31:55Z","timestamp":1694665915000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.12996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,17]]},"references-count":51,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/cns.12996"],"URL":"https:\/\/doi.org\/10.1111\/cns.12996","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,17]]},"assertion":[{"value":"2018-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-05-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}