{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:44:02Z","timestamp":1790441042657,"version":"4.1.0"},"reference-count":49,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6805","funder":[{"DOI":"10.13039\/100008695","name":"Japan Foundation for Applied Enzymology","doi-asserted-by":"publisher","award":["23T002"],"award-info":[{"award-number":["23T002"]}],"id":[{"id":"10.13039\/100008695","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04919"],"award-info":[{"award-number":["22H04919"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP25K24598"],"award-info":[{"award-number":["JP25K24598"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06276"],"award-info":[{"award-number":["16H06276"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JPMJER1702"],"award-info":[{"award-number":["JPMJER1702"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,6,25]]},"abstract":"<jats:p>Impairments in intracellular quality-control mechanisms, including autophagy, affect neuronal integrity and function. Despite numerous studies aimed at slowing neuronal deterioration, it remains unclear whether neuronal function and intracellular quality can be restored once impaired. We developed a mouse model in which autophagy could be rapidly and reversibly regulated to investigate the reversibility of such defects. Suppressing autophagy led to proteome and transcriptome changes, inclusion body accumulation, and axonal swelling, all of which were largely ameliorated after autophagy restoration. Consistent with these cellular abnormalities, autophagy suppression induced motor and cognitive dysfunction, which was also reversed on autophagy restoration. Our findings elucidate the potential resilience of neuronal function and quality enabled by intracellular clearance.<\/jats:p>","DOI":"10.1126\/science.ady3911","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:00:46Z","timestamp":1782410446000},"page":"1363-1368","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Reversible suppression of autophagy in a mouse model reveals neuronal resilience"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0706-5400","authenticated-orcid":true,"given":"Tomoya","family":"Eguchi","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8534-2138","authenticated-orcid":true,"given":"Manabu","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan."},{"name":"Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4568-9940","authenticated-orcid":true,"given":"Takuya","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Protein Metabolism, Institute of Medical Science, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0860-8371","authenticated-orcid":true,"given":"Hideaki","family":"Morishita","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9202-5453","authenticated-orcid":true,"given":"Yasushi","family":"Saeki","sequence":"additional","affiliation":[{"name":"Division of Protein Metabolism, Institute of Medical Science, The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8091-8879","authenticated-orcid":true,"given":"Kenji","family":"Sakimura","sequence":"additional","affiliation":[{"name":"Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2511-0057","authenticated-orcid":true,"given":"Kenji F.","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Brain Sciences, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6258-6444","authenticated-orcid":true,"given":"Noboru","family":"Mizushima","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo, Japan."},{"name":"International Research Center for Neurointelligence (WPI-IRCN), The University of Tokyo, Institutes for Advanced Study (UTIAS), The University of Tokyo, Tokyo, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1886"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0003-4"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-022-00562-w"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04724"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04723"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.072389"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00588-3"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1362"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1206362109"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.3402\/pba.v5.28743"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI73938"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1458172"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14187-x"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2022.2052588"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2009.12.020"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.7.9296"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.5.5.8249"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200604129"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01005-15"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.108477"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0888-7543(03)00032-6"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200712064"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.10.005"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.05.011"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01356-4"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47440-z"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.05.010"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-024-01196-4"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.283416.116"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2022.10.008"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112372"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701311104"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4964"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2202016119"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28301-z"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2368335"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2018.12.021"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80623-6"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1460-x"},{"key":"e_1_3_2_42_2","unstructured":"T. Eguchi. Reversible suppression of autophagy in a mouse model reveals neuronal resilience. Dryad (2026); https:\/\/doi.org\/10.5061\/dryad.3bk3j9m1b."},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2007.01.004"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2377"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-019-0638-x"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq054"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkad347"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1039\/B714176A"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1039\/C0MB00141D"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-009-0178-y"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.ady3911","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T18:01:31Z","timestamp":1782410491000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.ady3911"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":49,"journal-issue":{"issue":"6805","published-print":{"date-parts":[[2026,6,25]]}},"alternative-id":["10.1126\/science.ady3911"],"URL":"https:\/\/doi.org\/10.1126\/science.ady3911","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"assertion":[{"value":"2025-04-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-05","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-08","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}