{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:23:25Z","timestamp":1791404605304,"version":"4.3.3"},"reference-count":123,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,4]],"date-time":"2025-05-04T00:00:00Z","timestamp":1746316800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22ek0109426"],"award-info":[{"award-number":["JP22ek0109426"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm0425014"],"award-info":[{"award-number":["JP24wm0425014"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm0625301"],"award-info":[{"award-number":["JP24wm0625301"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005865","name":"Mochida Memorial Foundation for Medical and Pharmaceutical Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004088","name":"Kowa Life Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004088","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008273","name":"Novartis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008273","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioEssays"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Recent evidence indicates that the mitochondria\u2013endoplasmic reticulum (ER) contact site is a novel microdomain essential for cellular homeostasis. Various proteins are accumulated at the mitochondria\u2010associated membrane (MAM), an ER subcomponent closely associated with the mitochondria, contributing to Ca<jats:sup>2+<\/jats:sup> transfer to the mitochondria, lipid synthesis, mitochondrial fission\/fusion, and autophagy. These functions are disrupted in the diseases, particularly in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Alzheimer's disease. In this review, we summarize the disruption of protein homeostasis in various neurodegenerative diseases, present recent works on the mechanisms of MAM aberration, including ours mainly focused on ALS, and then discuss challenges and prospects for future MAM\u2010targeted therapies in neurodegenerative diseases.<\/jats:p>","DOI":"10.1002\/bies.70016","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T02:58:11Z","timestamp":1746413891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases"],"prefix":"10.1002","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8038-7919","authenticated-orcid":false,"given":"Seiji","family":"Watanabe","sequence":"first","affiliation":[{"name":"Department of Neuroscience and Pathobiology Research Institute of Environmental Medicine Nagoya University  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4655-0035","authenticated-orcid":false,"given":"Koji","family":"Yamanaka","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pathobiology Research Institute of Environmental Medicine Nagoya University  Nagoya Aichi Japan"},{"name":"Department of Neuroscience and Pathobiology Nagoya University Graduate School of Medicine  Nagoya Aichi Japan"},{"name":"Institute for Glyco\u2010core Research (iGCORE) Nagoya University  Nagoya Aichi Japan"},{"name":"Center for One Medicine Innovative Translational Research (COMIT) Nagoya University  Nagoya Aichi Japan"},{"name":"Research Institute for Quantum and Chemical Innovation Institutes of Innovation for Future Society Nagoya University  Nagoya Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,4]]},"reference":[{"key":"e_1_2_19_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.988014"},{"key":"e_1_2_19_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-00705-8"},{"key":"e_1_2_19_4_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.248534"},{"key":"e_1_2_19_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2020.102343"},{"key":"e_1_2_19_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39106-9"},{"key":"e_1_2_19_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.10.007"},{"key":"e_1_2_19_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2014.12.011"},{"key":"e_1_2_19_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106031"},{"key":"e_1_2_19_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09291-x"},{"key":"e_1_2_19_11_1","doi-asserted-by":"publisher","DOI":"10.26508\/lsa.201900308"},{"key":"e_1_2_19_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11910"},{"key":"e_1_2_19_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00595"},{"key":"e_1_2_19_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2020.01.017"},{"key":"e_1_2_19_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay2494"},{"key":"e_1_2_19_16_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2022774"},{"key":"e_1_2_19_17_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108863"},{"key":"e_1_2_19_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092022"},{"key":"e_1_2_19_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13615"},{"key":"e_1_2_19_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1908722"},{"key":"e_1_2_19_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.04.021"},{"key":"e_1_2_19_22_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2024.2413313"},{"key":"e_1_2_19_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2019.1586248"},{"key":"e_1_2_19_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.243"},{"key":"e_1_2_19_25_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2020.1749490"},{"key":"e_1_2_19_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-05091-2"},{"key":"e_1_2_19_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.74"},{"key":"e_1_2_19_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111899"},{"key":"e_1_2_19_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.769213"},{"key":"e_1_2_19_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.08.036"},{"key":"e_1_2_19_31_1","doi-asserted-by":"crossref","DOI":"10.1101\/cshperspect.a041247","article-title":"Endoplasmic Reticulum\u2010Associated Protein Degradation","volume":"14","author":"Krshnan L.","year":"2022","journal-title":"Cold Spring Harbor Perspectives in Biology"},{"key":"e_1_2_19_32_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1640108"},{"key":"e_1_2_19_33_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2315347120"},{"key":"e_1_2_19_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118876"},{"key":"e_1_2_19_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2020.12.005"},{"key":"e_1_2_19_36_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20210024"},{"key":"e_1_2_19_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa076"},{"key":"e_1_2_19_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.03.003"},{"key":"e_1_2_19_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112025"},{"key":"e_1_2_19_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.12.032"},{"key":"e_1_2_19_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5314"},{"key":"e_1_2_19_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-019-0244-7"},{"key":"e_1_2_19_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2021.112474"},{"key":"e_1_2_19_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(22)01272-7"},{"key":"e_1_2_19_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.07.033"},{"key":"e_1_2_19_46_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abq5622"},{"key":"e_1_2_19_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0293-z"},{"key":"e_1_2_19_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0300-4"},{"key":"e_1_2_19_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04424-7"},{"key":"e_1_2_19_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04436-3"},{"key":"e_1_2_19_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3002028"},{"key":"e_1_2_19_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.08.022"},{"key":"e_1_2_19_53_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020106389"},{"key":"e_1_2_19_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1926656"},{"key":"e_1_2_19_55_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.772226"},{"key":"e_1_2_19_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-019-02832-2"},{"key":"e_1_2_19_57_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022850"},{"key":"e_1_2_19_58_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf6895"},{"key":"e_1_2_19_59_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2022111719"},{"key":"e_1_2_19_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052776"},{"key":"e_1_2_19_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.471"},{"key":"e_1_2_19_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2021.04.008"},{"key":"e_1_2_19_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.04.010"},{"key":"e_1_2_19_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.09.181"},{"key":"e_1_2_19_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2023.104798"},{"key":"e_1_2_19_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2015.10.006"},{"key":"e_1_2_19_67_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200908164"},{"key":"e_1_2_19_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.459"},{"key":"e_1_2_19_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14285"},{"key":"e_1_2_19_70_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20122942"},{"key":"e_1_2_19_71_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2018.1535292"},{"key":"e_1_2_19_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2023.166716"},{"key":"e_1_2_19_73_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201606403"},{"key":"e_1_2_19_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4996"},{"key":"e_1_2_19_75_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201541726"},{"key":"e_1_2_19_76_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202100137R"},{"key":"e_1_2_19_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)32205-4"},{"key":"e_1_2_19_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00391-w"},{"key":"e_1_2_19_79_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01249-0"},{"key":"e_1_2_19_80_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-021-00278-7"},{"key":"e_1_2_19_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-01929-y"},{"key":"e_1_2_19_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_19_83_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_2_19_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2019.04.022"},{"key":"e_1_2_19_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2020.11.015"},{"key":"e_1_2_19_86_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-022-01457-x"},{"key":"e_1_2_19_87_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1113694"},{"key":"e_1_2_19_88_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0197-x"},{"key":"e_1_2_19_89_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601309"},{"key":"e_1_2_19_90_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090219"},{"key":"e_1_2_19_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2012.202"},{"key":"e_1_2_19_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.105020"},{"key":"e_1_2_19_93_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201796797"},{"key":"e_1_2_19_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.07.011"},{"key":"e_1_2_19_95_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11041011"},{"key":"e_1_2_19_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00218-X"},{"key":"e_1_2_19_97_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-022-02851-1"},{"key":"e_1_2_19_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2016.04.042"},{"key":"e_1_2_19_99_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024240"},{"key":"e_1_2_19_100_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00077"},{"key":"e_1_2_19_101_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2018.08.010"},{"key":"e_1_2_19_102_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2019.00020"},{"key":"e_1_2_19_103_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-4567-7_12"},{"key":"e_1_2_19_104_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23020780"},{"key":"e_1_2_19_105_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1171440"},{"key":"e_1_2_19_106_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2020.104741"},{"key":"e_1_2_19_107_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512511"},{"key":"e_1_2_19_108_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28769-9"},{"key":"e_1_2_19_109_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-017-0079-3"},{"key":"e_1_2_19_110_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1906565116"},{"key":"e_1_2_19_111_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2013.01.034"},{"key":"e_1_2_19_112_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.100760"},{"key":"e_1_2_19_113_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2024.115109"},{"key":"e_1_2_19_114_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318-024-00036-1"},{"key":"e_1_2_19_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2013.12.005"},{"key":"e_1_2_19_116_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.780588"},{"key":"e_1_2_19_117_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-012-0140-y"},{"key":"e_1_2_19_118_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241512025"},{"key":"e_1_2_19_119_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-023-03960-6"},{"key":"e_1_2_19_120_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2022.105857"},{"key":"e_1_2_19_121_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15366"},{"key":"e_1_2_19_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30391-0"},{"key":"e_1_2_19_123_1","doi-asserted-by":"publisher","DOI":"10.17925\/USN.2023.19.2.3"},{"key":"e_1_2_19_124_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-024-01742-x"}],"container-title":["BioEssays"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bies.70016","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T08:58:52Z","timestamp":1753088332000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bies.70016"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,4]]},"references-count":123,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1002\/bies.70016"],"URL":"https:\/\/doi.org\/10.1002\/bies.70016","archive":["Portico"],"relation":{},"ISSN":["0265-9247","1521-1878"],"issn-type":[{"value":"0265-9247","type":"print"},{"value":"1521-1878","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,4]]},"assertion":[{"value":"2024-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70016"}}