{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T21:52:50Z","timestamp":1790632370910,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T00:00:00Z","timestamp":1616371200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI16C0947"],"award-info":[{"award-number":["HI16C0947"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI16C0947"],"award-info":[{"award-number":["HI16C0947"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI16C0947"],"award-info":[{"award-number":["HI16C0947"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Impairment of protein clearance mechanisms leads to \u03b1\u2010synuclein accumulation in dopaminergic neurons, contributing to the pathogenesis of Parkinson's disease (PD). Based on the finding that Fas\u2010associated factor 1 (FAF1), a positive modulator of PD, colocalizes with \u03b1\u2010synuclein in PD patient brains, we investigated the existence of pathological interplay between FAF1 and \u03b1\u2010synuclein. Monomeric and high\u2010molecular\u2010weight forms of \u03b1\u2010synuclein were increased in FAF1\u2010overexpressing SH\u2010SY5Y cells. In particular, \u03b1\u2010synuclein turnover was accelerated by genetic depletion of FAF1 in SH\u2010SY5Y cells. Therefore, we questioned whether FAF1 is involved in the \u03b1\u2010synuclein clearance process. Autophagy inhibitors, but not proteasome inhibitors, restored concurrent attenuation of \u03b1\u2010synuclein expression by FAF1 depletion in SH\u2010SY5Y cells. Moreover, we found alterations in autophagy markers in SH\u2010SY5Y cells caused by FAF1 overexpression, indicating that FAF1 disturbed \u03b1\u2010synuclein clearance through the autophagy\u2010lysosome pathway. Indeed, FAF1 activated the mammalian target of rapamycin (mTOR) pathway, subsequently suppressing autophagosome formation. Consistently, \u03b1\u2010synuclein\u2010mediated mitochondrial dysfunction was observed in FAF1\u2010overexpressing SH\u2010SY5Y cells. Furthermore, FAF1 overexpression using stereotaxic injection of adeno\u2010associated virus led to \u03b1\u2010synuclein accumulation and autophagy dysregulation in the PD model mice. Taken together, our results reveal a novel role for FAF1: that of a negative regulator of autophagic \u03b1\u2010synuclein clearance.<\/jats:p>","DOI":"10.1096\/fj.202001371rr","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T09:30:52Z","timestamp":1616405452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fas\u2010associated factor 1 induces the accumulation of \u03b1\u2010synuclein through autophagic suppression in dopaminergic neurons"],"prefix":"10.1096","volume":"35","author":[{"given":"Bok\u2010Seok","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Chungnam National University Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taeik","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Chungnam National University Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Eun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Kainos Medicine, Inc. Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jae Moon","family":"Lee","sequence":"additional","affiliation":[{"name":"Kainos Medicine, Inc. Seongnam South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunhee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Chungnam National University Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,22]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0733-8619(05)70259-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.22.1.123"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1087753"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-014-0073-2"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06900.x"},{"key":"e_1_2_9_8_1","first-page":"879","article-title":"Aggregation of alpha\u2010synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy bodies","volume":"152","author":"Baba M","year":"1998","journal-title":"Am J Pathol"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22524"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7217-5"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.023"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4269"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.1999.tb00554.x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000271080.53272.c7"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.21007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.5607\/en.2013.22.2.77"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.06.022"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112457"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2016.09.003"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M710012200"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02263"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1717"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-012-8341-2"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300227200"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3809-03.2004"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1560-11.2011"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0034713"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.16.9280"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15021"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302200200"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C700106200"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006398"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804199200"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.6.2511-2524.2005"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2016.99"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt006"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2008.05.006"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201003122"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00575-1"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18091865"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aan5850"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.095216"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00833-4"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8394-x"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.02.056"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000000871"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-38500-2"},{"key":"e_1_2_9_48_1","first-page":"561","article-title":"Concentration\u2010dependent effects of proteasomal inhibition on tau processing in a cellular model of tauopathy","volume":"2","author":"Hamano T","year":"2009","journal-title":"Int J Clin Exp Pathol"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp367"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/35087056"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695148"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.11.004"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060627"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1001-1144"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073235"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.73"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.198"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2013.12.017"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M400255200"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.07.012"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101738"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406297200"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040361"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0060184"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2015.4198"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.09.044"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat8407"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202001371RR","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202001371RR","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202001371RR","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T17:17:10Z","timestamp":1761671830000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202001371RR"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,22]]},"references-count":66,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1096\/fj.202001371RR"],"URL":"https:\/\/doi.org\/10.1096\/fj.202001371rr","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,22]]},"assertion":[{"value":"2020-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-22","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e21363"}}