{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:10:36Z","timestamp":1789704636865,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T00:00:00Z","timestamp":1782432000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18H02743"],"award-info":[{"award-number":["18H02743"]}],"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":["25K10801"],"award-info":[{"award-number":["25K10801"]}],"id":[{"id":"10.13039\/501100001691","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"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2026,8]]},"abstract":"ABSTRACT<\/jats:title>\n \n Aims<\/jats:title>\n \n Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with unclear molecular mechanisms. Heterozygous protein\u2010truncating variants of\n DNAJC7<\/jats:italic>\n , which encode a cochaperone involved in Hsp70\/90\u2010mediated protein quality control, are potential risk factors for ALS. However, the neuropathological consequences of heterozygous\n DNAJC7<\/jats:italic>\n mutations are unclear. We aimed to clarify the molecular and neuropathological features associated with a heterozygous\n DNAJC7<\/jats:italic>\n mutation in ALS.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We genetically screened 39 Japanese patients with ALS and identified a novel heterozygous frameshift mutation in\n DNAJC7<\/jats:italic>\n (c.157_163del, p.Lys53Ter) in one patient that was neuropathologically diagnosed with Kii ALS. We performed biochemical and neuropathological analyses using postmortem tissues from this patient, from cases of ALS without the mutation and from control cases.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In the cases of ALS without\n DNAJC7<\/jats:italic>\n mutation, there was elevation of both\n DNAJC7<\/jats:italic>\n mRNA and protein levels compared with controls. The patient with\n DNAJC7<\/jats:italic>\n mutation showed relatively lower\n DNAJC7<\/jats:italic>\n mRNA and protein levels compared with the nonmutated cases of ALS, although mRNA expression remained relatively higher.\n DNAJC7<\/jats:italic>\n may be upregulated as a protective response against ALS pathogenesis, whereas a heterozygous mutation may attenuate this response. Immunohistochemistry and double immunofluorescence demonstrated partial colocalization of DNAJC7 with phospho\u2010TDP\u201043\u2010positive neuronal cytoplasmic inclusions, which supports a direct role for\n DNAJC7<\/jats:italic>\n in modulating pathological TDP\u201043 aggregation.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings provide neuropathological evidence linking heterozygous\n DNAJC7<\/jats:italic>\n mutation to ALS, demonstrating impaired protein expression and suggesting a loss\u2010of\u2010function mechanism that compromises protective responses to TDP\u201043 pathology.\n DNAJC7<\/jats:italic>\n may represent a key modulator of ALS pathogenesis and potential therapeutic target.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/nan.70086","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T02:14:49Z","timestamp":1782526489000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuropathological and Molecular Features Associated With a Heterozygous\n DNAJC7<\/i>\n Mutation in Amyotrophic Lateral Sclerosis"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3010-7741","authenticated-orcid":false,"given":"Yoshiaki","family":"Nakayama","sequence":"first","affiliation":[{"name":"Department of Neurology Wakayama Medical University Wakayama City Wakayama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kodai","family":"Kume","sequence":"additional","affiliation":[{"name":"Department of Molecular Epidemiology, Research Institute for Radiation Biology and Medicine Hiroshima University Hiroshima 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