{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T13:29:19Z","timestamp":1782826159955,"version":"3.54.5"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23K08543"],"award-info":[{"award-number":["JP23K08543"]}],"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":["JP23K10450"],"award-info":[{"award-number":["JP23K10450"]}],"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":["JP23K27514"],"award-info":[{"award-number":["JP23K27514"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24wm0425019"],"award-info":[{"award-number":["JP24wm0425019"]}],"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":["JP23ek0109673"],"award-info":[{"award-number":["JP23ek0109673"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013171","name":"Ryobi Teien Memory Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012330","name":"Okayama University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100012330","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the progressive degeneration of motor neurons. ALS pathology primarily involves the failure of protein quality control mechanisms, leading to the accumulation of misfolded proteins, particularly TAR DNA-binding protein 43 (TDP-43). TDP-43 aggregation is a central pathological feature of ALS. Maintaining protein homeostasis is critical and facilitated by heat shock proteins (HSPs), particularly the HSP40 family, which includes co-chaperones such as DNAJC7. Here, we report a family with three siblings affected by ALS who carry a homozygous c.518dupC frameshift variant in <jats:italic>DNAJC7<\/jats:italic>, a member of the HSP40 family. All three patients exhibited progressive muscle weakness, limb atrophy, bulbar palsy, and respiratory failure. Pathological examination revealed degeneration of both upper and lower motor neurons, with phosphorylated TDP-43-positive neuronal cytoplasmic inclusions in the frontal and temporal cortices. Immunoblot analysis were consistent with a type B pattern of phosphorylated TDP-43 in the precentral gyrus. Immunohistochemistry and RNA sequencing analyses demonstrated a substantial reduction in <jats:italic>DNAJC7<\/jats:italic> expression at both the protein and RNA levels in affected brain regions. In a TDP-43 cell model, <jats:italic>DNAJC7<\/jats:italic> knockdown impaired the disassembly of TDP-43 following arsenite-induced stress, whereas <jats:italic>DNAJC7<\/jats:italic> overexpression suppressed the assembly and promoted the disassembly of arsenite-induced TDP-43 condensates. Furthermore, in a zebrafish ALS model, <jats:italic>dnajc7<\/jats:italic> knockdown resulted in increased TDP-43 aggregation in motor neurons and reduced survival. To the best of our knowledge, this study provides the first evidence linking biallelic loss-of-function variants in <jats:italic>DNAJC7<\/jats:italic> to familial ALS with TDP-43 pathology.<\/jats:p>","DOI":"10.1007\/s00401-025-02899-y","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:22:18Z","timestamp":1755069738000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Biallelic variants in DNAJC7 cause familial amyotrophic lateral sclerosis with the TDP-43 pathology"],"prefix":"10.1007","volume":"150","author":[{"given":"Toru","family":"Yamashita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Yokota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiki","family":"Ousaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Haraguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Satoshi","family":"Ota-Elliott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chika","family":"Matsuoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Kawano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanae","family":"Nakashima-Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Fukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumiko","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuta","family":"Morihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuyuki","family":"Hosono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seishi","family":"Terada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Takaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Ishiura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"2899_CR1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/ng1293-323","volume":"5","author":"M Aoki","year":"1993","unstructured":"Aoki M, Ogasawara M, Matsubara Y, Narisawa K, Nakamura S, Itoyama Y et al (1993) Mild ALS in Japan associated with novel SOD mutation. Nat Genet 5:323\u2013324. https:\/\/doi.org\/10.1038\/ng1293-323","journal-title":"Nat Genet"},{"key":"2899_CR2","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.bbrc.2006.10.093","volume":"351","author":"T Arai","year":"2006","unstructured":"Arai T, Hasegawa M, Akiyama H, Ikeda K, Nonaka T, Mori H et al (2006) TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Biochem Biophys Res Commun 351:602\u2013611. https:\/\/doi.org\/10.1016\/j.bbrc.2006.10.093","journal-title":"Biochem Biophys Res Commun"},{"key":"2899_CR3","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1038\/s41586-021-04199-3","volume":"601","author":"D Arseni","year":"2022","unstructured":"Arseni D, Hasegawa M, Murzin AG, Kametani F, Arai M, Yoshida M et al (2022) Structure of pathological TDP-43 filaments from ALS with FTLD. Nature 601:139\u2013143. https:\/\/doi.org\/10.1038\/s41586-021-04199-3","journal-title":"Nature"},{"key":"2899_CR4","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/s41586-024-08024-5","volume":"634","author":"D Arseni","year":"2024","unstructured":"Arseni D, Nonaka T, Jacobsen MH, Murzin AG, Cracco L, Peak-Chew SY et al (2024) Heteromeric amyloid filaments of ANXA11 and TDP-43 in FTLD-TDP type C. Nature 634:662\u2013668. https:\/\/doi.org\/10.1038\/s41586-024-08024-5","journal-title":"Nature"},{"key":"2899_CR5","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/s41467-020-14815-x","volume":"11","author":"K Asakawa","year":"2020","unstructured":"Asakawa K, Handa H, Kawakami K (2020) Optogenetic modulation of TDP-43 oligomerization accelerates ALS-related pathologies in the spinal motor neurons. Nat Commun 11:1004. https:\/\/doi.org\/10.1038\/s41467-020-14815-x","journal-title":"Nat Commun"},{"key":"2899_CR6","doi-asserted-by":"publisher","first-page":"104639","DOI":"10.1016\/j.nbd.2019.104639","volume":"134","author":"Y Baradaran-Heravi","year":"2020","unstructured":"Baradaran-Heravi Y, Van Broeckhoven C, van der Zee J (2020) Stress granule mediated protein aggregation and underlying gene defects in the FTD-ALS spectrum. Neurobiol Dis 134:104639. https:\/\/doi.org\/10.1016\/j.nbd.2019.104639","journal-title":"Neurobiol Dis"},{"key":"2899_CR7","doi-asserted-by":"publisher","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","volume":"30","author":"AM Bolger","year":"2014","unstructured":"Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30:2114\u20132120. https:\/\/doi.org\/10.1093\/bioinformatics\/btu170","journal-title":"Bioinformatics"},{"key":"2899_CR8","doi-asserted-by":"publisher","first-page":"102840","DOI":"10.1016\/j.jbc.2022.102840","volume":"299","author":"JEA Braun","year":"2023","unstructured":"Braun JEA (2023) Extracellular chaperone networks and the export of J-domain proteins. J Biol Chem 299:102840. https:\/\/doi.org\/10.1016\/j.jbc.2022.102840","journal-title":"J Biol Chem"},{"key":"2899_CR9","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1016\/j.celrep.2014.09.042","volume":"9","author":"M Brehme","year":"2014","unstructured":"Brehme M, Voisine C, Rolland T, Wachi S, Soper JH, Zhu Y et al (2014) A chaperome subnetwork safeguards proteostasis in aging and neurodegenerative disease. Cell Rep 9:1135\u20131150. https:\/\/doi.org\/10.1016\/j.celrep.2014.09.042","journal-title":"Cell Rep"},{"key":"2899_CR10","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown RH, Al-Chalabi A (2017) Amyotrophic lateral sclerosis. N Engl J Med 377:162\u2013172. https:\/\/doi.org\/10.1056\/NEJMra1603471","journal-title":"N Engl J Med"},{"key":"2899_CR11","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1089\/zeb.2022.0043","volume":"20","author":"S Cao","year":"2023","unstructured":"Cao S, Dong Z, Dong X, Jia W, Zhou F, Zhao Q (2023) Zebrafish sox2 is required for the swim bladder inflation by controlling the swim-up behavior. Zebrafish 20:10\u201318. https:\/\/doi.org\/10.1089\/zeb.2022.0043","journal-title":"Zebrafish"},{"key":"2899_CR12","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1089\/zeb.2022.0043","volume":"20","author":"SS Cao","year":"2023","unstructured":"Cao SS, Dong ZJ, Dong XH, Jia WS, Zhou FY, Zhao QS (2023) Zebrafish is required for the swim bladder inflation by controlling the swim-up behavior. Zebrafish 20:10\u201318. https:\/\/doi.org\/10.1089\/zeb.2022.0043","journal-title":"Zebrafish"},{"key":"2899_CR13","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/s41467-023-36023-z","volume":"14","author":"J Carrasco","year":"2023","unstructured":"Carrasco J, Anton R, Valbuena A, Pantoja-Uceda D, Mukhi M, Hervas R et al (2023) Metamorphism in TDP-43 prion-like domain determines chaperone recognition. Nat Commun 14:466. https:\/\/doi.org\/10.1038\/s41467-023-36023-z","journal-title":"Nat Commun"},{"key":"2899_CR14","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1093\/brain\/aww028","volume":"139","author":"HJ Chen","year":"2016","unstructured":"Chen HJ, Mitchell JC, Novoselov S, Miller J, Nishimura AL, Scotter EL et al (2016) The heat shock response plays an important role in TDP-43 clearance: evidence for dysfunction in amyotrophic lateral sclerosis. Brain 139:1417\u20131432. https:\/\/doi.org\/10.1093\/brain\/aww028","journal-title":"Brain"},{"key":"2899_CR15","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1093\/bioinformatics\/btv710","volume":"32","author":"X Chen","year":"2016","unstructured":"Chen X, Schulz-Trieglaff O, Shaw R, Barnes B, Schlesinger F, Kallberg M et al (2016) Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics 32:1220\u20131222. https:\/\/doi.org\/10.1093\/bioinformatics\/btv710","journal-title":"Bioinformatics"},{"key":"2899_CR16","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.neuron.2011.09.011","volume":"72","author":"M DeJesus-Hernandez","year":"2011","unstructured":"DeJesus-Hernandez M, Mackenzie IR, Boeve BF, Boxer AL, Baker M, Rutherford NJ et al (2011) Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 72:245\u2013256. https:\/\/doi.org\/10.1016\/j.neuron.2011.09.011","journal-title":"Neuron"},{"key":"2899_CR17","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/ana.22051","volume":"67","author":"HX Deng","year":"2010","unstructured":"Deng HX, Zhai H, Bigio EH, Yan J, Fecto F, Ajroud K et al (2010) FUS-immunoreactive inclusions are a common feature in sporadic and non-SOD1 familial amyotrophic lateral sclerosis. Ann Neurol 67:739\u2013748. https:\/\/doi.org\/10.1002\/ana.22051","journal-title":"Ann Neurol"},{"key":"2899_CR18","doi-asserted-by":"publisher","first-page":"1966","DOI":"10.1038\/s41593-019-0530-0","volume":"22","author":"SMK Farhan","year":"2019","unstructured":"Farhan SMK, Howrigan DP, Abbott LE, Klim JR, Topp SD, Byrnes AE et al (2019) Exome sequencing in amyotrophic lateral sclerosis implicates a novel gene, DNAJC7, encoding a heat-shock protein. Nat Neurosci 22:1966\u20131974. https:\/\/doi.org\/10.1038\/s41593-019-0530-0","journal-title":"Nat Neurosci"},{"key":"2899_CR19","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1136\/jnnp-2018-319386","volume":"90","author":"K Forsberg","year":"2019","unstructured":"Forsberg K, Graffmo K, Pakkenberg B, Weber M, Nielsen M, Marklund S et al (2019) Misfolded SOD1 inclusions in patients with mutations in C9orf72 and other ALS\/FTD-associated genes. J Neurol Neurosurg Psychiatry 90:861\u2013869. https:\/\/doi.org\/10.1136\/jnnp-2018-319386","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2899_CR20","doi-asserted-by":"publisher","first-page":"e98186","DOI":"10.1371\/journal.pone.0098186","volume":"9","author":"JA Gagnon","year":"2014","unstructured":"Gagnon JA, Valen E, Thyme SB, Huang P, Akhmetova L, Pauli A et al (2014) Efficient mutagenesis by Cas9 protein-mediated oligonucleotide insertion and large-scale assessment of single-guide RNAs. PLoS ONE 9:e98186. https:\/\/doi.org\/10.1371\/journal.pone.0098186","journal-title":"PLoS ONE"},{"key":"2899_CR21","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.neuron.2019.02.038","volume":"102","author":"F Gasset-Rosa","year":"2019","unstructured":"Gasset-Rosa F, Lu S, Yu H, Chen C, Melamed Z, Guo L et al (2019) Cytoplasmic TDP-43 de-mixing independent of stress granules drives inhibition of nuclear import, loss of nuclear TDP-43, and cell death. Neuron 102:339-357.e337. https:\/\/doi.org\/10.1016\/j.neuron.2019.02.038","journal-title":"Neuron"},{"key":"2899_CR22","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1038\/s41422-021-00526-5","volume":"31","author":"J Gu","year":"2021","unstructured":"Gu J, Wang C, Hu R, Li Y, Zhang S, Sun Y et al (2021) Hsp70 chaperones TDP-43 in dynamic, liquid-like phase and prevents it from amyloid aggregation. Cell Res 31:1024\u20131027. https:\/\/doi.org\/10.1038\/s41422-021-00526-5","journal-title":"Cell Res"},{"key":"2899_CR23","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1038\/ng1005-1015","volume":"37","author":"DF Gudbjartsson","year":"2005","unstructured":"Gudbjartsson DF, Thorvaldsson T, Kong A, Gunnarsson G, Ingolfsdottir A (2005) Allegro version 2. Nat Genet 37:1015\u20131016. https:\/\/doi.org\/10.1038\/ng1005-1015","journal-title":"Nat Genet"},{"key":"2899_CR24","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1002\/ana.21425","volume":"64","author":"M Hasegawa","year":"2008","unstructured":"Hasegawa M, Arai T, Nonaka T, Kametani F, Yoshida M, Hashizume Y et al (2008) Phosphorylated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Ann Neurol 64:60\u201370. https:\/\/doi.org\/10.1002\/ana.21425","journal-title":"Ann Neurol"},{"key":"2899_CR25","doi-asserted-by":"publisher","first-page":"314.e311","DOI":"10.1016\/j.neurobiolaging.2021.04.026","volume":"106","author":"J He","year":"2021","unstructured":"He J, Ma X, Yu W, Tang L, Fu J, Liu X et al (2021) Validation of the pathogenic role of rare DNAJC7 variants in Chinese patients with amyotrophic lateral sclerosis. Neurobiol Aging 106:314.e311-314.e316. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2021.04.026","journal-title":"Neurobiol Aging"},{"key":"2899_CR26","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1093\/jnen\/nlaa003","volume":"79","author":"K Ikenaka","year":"2020","unstructured":"Ikenaka K, Ishigaki S, Iguchi Y, Kawai K, Fujioka Y, Yokoi S et al (2020) Characteristic features of FUS inclusions in spinal motor neurons of sporadic amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 79:370\u2013377. https:\/\/doi.org\/10.1093\/jnen\/nlaa003","journal-title":"J Neuropathol Exp Neurol"},{"key":"2899_CR27","doi-asserted-by":"publisher","first-page":"609698","DOI":"10.3389\/fcell.2021.609698","volume":"9","author":"P Jeon","year":"2021","unstructured":"Jeon P, Lee JA (2021) Dr. Jekyll and Mr. Hyde? Physiology and pathology of neuronal stress granules. Front Cell Dev Biol 9:609698. https:\/\/doi.org\/10.3389\/fcell.2021.609698","journal-title":"Front Cell Dev Biol"},{"key":"2899_CR28","doi-asserted-by":"publisher","first-page":"e503","DOI":"10.1212\/NXG.0000000000000503","volume":"6","author":"KY Jih","year":"2020","unstructured":"Jih KY, Tsai PC, Tsai YS, Liao YC, Lee YC (2020) Rapid progressive ALS in a patient with a DNAJC7 loss-of-function mutation. Neurol Genet 6:e503. https:\/\/doi.org\/10.1212\/NXG.0000000000000503","journal-title":"Neurol Genet"},{"key":"2899_CR29","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/ng.132","volume":"40","author":"E Kabashi","year":"2008","unstructured":"Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C et al (2008) TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet 40:572\u2013574. https:\/\/doi.org\/10.1038\/ng.132","journal-title":"Nat Genet"},{"key":"2899_CR30","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1038\/nrm2941","volume":"11","author":"HH Kampinga","year":"2010","unstructured":"Kampinga HH, Craig EA (2010) The HSP70 chaperone machinery: J proteins as drivers of functional specificity. Nat Rev Mol Cell Biol 11:579\u2013592. https:\/\/doi.org\/10.1038\/nrm2941","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2899_CR31","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1038\/s41587-019-0201-4","volume":"37","author":"D Kim","year":"2019","unstructured":"Kim D, Paggi JM, Park C, Bennett C, Salzberg SL (2019) Graph-based genome alignment and genotyping with HISAT2 and HISAT-genotype. Nat Biotechnol 37:907\u2013915. https:\/\/doi.org\/10.1038\/s41587-019-0201-4","journal-title":"Nat Biotechnol"},{"key":"2899_CR32","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.3390\/cells12091302","volume":"12","author":"S Kinger","year":"2023","unstructured":"Kinger S, Dubey AR, Kumar P, Jagtap YA, Choudhary A, Kumar A et al (2023) Molecular chaperones\u2019 potential against defective proteostasis of amyotrophic lateral sclerosis. Cells 12:1302. https:\/\/doi.org\/10.3390\/cells12091302","journal-title":"Cells"},{"key":"2899_CR33","doi-asserted-by":"publisher","first-page":"1177","DOI":"10.1007\/s12192-018-0930-1","volume":"23","author":"A Kitamura","year":"2018","unstructured":"Kitamura A, Iwasaki N, Kinjo M (2018) Molecular chaperone HSP70 prevents formation of inclusion bodies of the 25-kDa C-terminal fragment of TDP-43 by preventing aggregate accumulation. Cell Stress Chaperones 23:1177\u20131183. https:\/\/doi.org\/10.1007\/s12192-018-0930-1","journal-title":"Cell Stress Chaperones"},{"key":"2899_CR34","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1126\/science.1166066","volume":"323","author":"TJ Kwiatkowski Jr","year":"2009","unstructured":"Kwiatkowski TJ Jr, Bosco DA, Leclerc AL, Tamrazian E, Vanderburg CR, Russ C et al (2009) Mutations in the FUS\/TLS gene on chromosome 16 cause familial amyotrophic lateral sclerosis. Science 323:1205\u20131208. https:\/\/doi.org\/10.1126\/science.1166066","journal-title":"Science"},{"key":"2899_CR35","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead B, Salzberg SL (2012) Fast gapped-read alignment with Bowtie 2. Nat Methods 9:357\u2013359. https:\/\/doi.org\/10.1038\/nmeth.1923","journal-title":"Nat Methods"},{"key":"2899_CR36","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1038\/s41556-022-00988-8","volume":"24","author":"S Lu","year":"2022","unstructured":"Lu S, Hu J, Arogundade OA, Goginashvili A, Vazquez-Sanchez S, Diedrich JK et al (2022) Heat-shock chaperone HSPB1 regulates cytoplasmic TDP-43 phase separation and liquid-to-gel transition. Nat Cell Biol 24:1378\u20131393. https:\/\/doi.org\/10.1038\/s41556-022-00988-8","journal-title":"Nat Cell Biol"},{"key":"2899_CR37","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/ana.21147","volume":"61","author":"IR Mackenzie","year":"2007","unstructured":"Mackenzie IR, Bigio EH, Ince PG, Geser F, Neumann M, Cairns NJ et al (2007) Pathological TDP-43 distinguishes sporadic amyotrophic lateral sclerosis from amyotrophic lateral sclerosis with SOD1 mutations. Ann Neurol 61:427\u2013434. https:\/\/doi.org\/10.1002\/ana.21147","journal-title":"Ann Neurol"},{"key":"2899_CR38","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.neuron.2019.01.048","volume":"102","author":"JR Mann","year":"2019","unstructured":"Mann JR, Gleixner AM, Mauna JC, Gomes E, DeChellis-Marks MR, Needham PG et al (2019) RNA binding antagonizes neurotoxic phase transitions of TDP-43. Neuron 102:321-338.e328. https:\/\/doi.org\/10.1016\/j.neuron.2019.01.048","journal-title":"Neuron"},{"key":"2899_CR39","doi-asserted-by":"publisher","first-page":"e73944","DOI":"10.1371\/journal.pone.0073944","volume":"8","author":"SS Novoselov","year":"2013","unstructured":"Novoselov SS, Mustill WJ, Gray AL, Dick JR, Kanuga N, Kalmar B et al (2013) Molecular chaperone mediated late-stage neuroprotection in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis. PLoS ONE 8:e73944. https:\/\/doi.org\/10.1371\/journal.pone.0073944","journal-title":"PLoS ONE"},{"key":"2899_CR40","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1038\/nbt.3122","volume":"33","author":"M Pertea","year":"2015","unstructured":"Pertea M, Pertea GM, Antonescu CM, Chang TC, Mendell JT, Salzberg SL (2015) StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol 33:290\u2013295. https:\/\/doi.org\/10.1038\/nbt.3122","journal-title":"Nat Biotechnol"},{"key":"2899_CR41","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.neuron.2011.09.010","volume":"72","author":"AE Renton","year":"2011","unstructured":"Renton AE, Majounie E, Waite A, Simon-Sanchez J, Rollinson S, Gibbs JR et al (2011) A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 72:257\u2013268. https:\/\/doi.org\/10.1016\/j.neuron.2011.09.010","journal-title":"Neuron"},{"key":"2899_CR42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/362059a0","volume":"362","author":"DR Rosen","year":"1993","unstructured":"Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A et al (1993) Mutations in Cu\/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59\u201362. https:\/\/doi.org\/10.1038\/362059a0","journal-title":"Nature"},{"key":"2899_CR43","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.nbd.2007.12.002","volume":"30","author":"PS Sharp","year":"2008","unstructured":"Sharp PS, Akbar MT, Bouri S, Senda A, Joshi K, Chen HJ et al (2008) Protective effects of heat shock protein 27 in a model of ALS occur in the early stages of disease progression. Neurobiol Dis 30:42\u201355. https:\/\/doi.org\/10.1016\/j.nbd.2007.12.002","journal-title":"Neurobiol Dis"},{"key":"2899_CR44","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1126\/science.1154584","volume":"319","author":"J Sreedharan","year":"2008","unstructured":"Sreedharan J, Blair IP, Tripathi VB, Hu X, Vance C, Rogelj B et al (2008) TDP-43 mutations in familial and sporadic amyotrophic lateral sclerosis. Science 319:1668\u20131672. https:\/\/doi.org\/10.1126\/science.1154584","journal-title":"Science"},{"key":"2899_CR45","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1080\/21678421.2020.1813314","volume":"22","author":"X Sun","year":"2021","unstructured":"Sun X, Zhao X, Liu Q, Zhang K, Liu S, Wang Z et al (2021) Mutations of DNAJC7 are rare in Chinese amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener 22:312\u2013315. https:\/\/doi.org\/10.1080\/21678421.2020.1813314","journal-title":"Amyotroph Lateral Scler Frontotemporal Degener"},{"key":"2899_CR46","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1056\/NEJMoa1212115","volume":"369","author":"The Multiple System Atrophy Research Collaboration","year":"2013","unstructured":"The Multiple System Atrophy Research Collaboration (2013) Mutations in COQ2 in familial and sporadic multiple-system atrophy. N Engl J Med 369:233\u2013244. https:\/\/doi.org\/10.1056\/NEJMoa1212115","journal-title":"N Engl J Med"},{"key":"2899_CR47","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.neurobiolaging.2021.12.002","volume":"113","author":"G Tohnai","year":"2022","unstructured":"Tohnai G, Nakamura R, Atsuta N, Nakatochi M, Hayashi N, Ito D et al (2022) Mutation screening of the DNAJC7 gene in Japanese patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging 113:131\u2013136. https:\/\/doi.org\/10.1016\/j.neurobiolaging.2021.12.002","journal-title":"Neurobiol Aging"},{"key":"2899_CR48","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.1165942","volume":"323","author":"C Vance","year":"2009","unstructured":"Vance C, Rogelj B, Hortobagyi T, De Vos KJ, Nishimura AL, Sreedharan J et al (2009) Mutations in FUS, an RNA processing protein, cause familial amyotrophic lateral sclerosis type 6. Science 323:1208\u20131211. https:\/\/doi.org\/10.1126\/science.1165942","journal-title":"Science"},{"key":"2899_CR49","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1109\/Ipdps.2019.00041","volume":"2019","author":"M Vasimuddin","year":"2019","unstructured":"Vasimuddin M, Misra S, Li H, Aluru S (2019) Efficient architecture-aware acceleration of BWA-MEM for Multicore Systems. Int Parall Distrib Process 2019:314\u2013324. https:\/\/doi.org\/10.1109\/Ipdps.2019.00041","journal-title":"Int Parall Distrib Process"},{"key":"2899_CR50","doi-asserted-by":"publisher","first-page":"e164","DOI":"10.1093\/nar\/gkq603","volume":"38","author":"K Wang","year":"2010","unstructured":"Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38:e164. https:\/\/doi.org\/10.1093\/nar\/gkq603","journal-title":"Nucleic Acids Res"},{"key":"2899_CR51","doi-asserted-by":"publisher","first-page":"821","DOI":"10.3389\/fgene.2020.00821","volume":"11","author":"M Wang","year":"2020","unstructured":"Wang M, Liu Z, Yuan Y, Ni J, Li W, Hu Y et al (2020) A novel potentially pathogenic rare variant in the DNAJC7 gene identified in amyotrophic lateral sclerosis patients from Mainland China. Front Genet 11:821. https:\/\/doi.org\/10.3389\/fgene.2020.00821","journal-title":"Front Genet"},{"key":"2899_CR52","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1007\/s12035-023-03677-1","volume":"61","author":"S Wang","year":"2024","unstructured":"Wang S, Zheng X, Wei Q, Lin J, Yang T, Xiao Y et al (2024) Rare DNAJC7 variants may play a minor role in Chinese patients with ALS. Mol Neurobiol 61:2265\u20132269. https:\/\/doi.org\/10.1007\/s12035-023-03677-1","journal-title":"Mol Neurobiol"},{"key":"2899_CR53","unstructured":"Westerfield M (1993) The zebrafish book: a guide for the laboratory use of zebrafish (Brachydanio rerio). M. Westerfield, City"},{"key":"2899_CR54","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1007\/s00401-009-0493-4","volume":"117","author":"O Yokota","year":"2009","unstructured":"Yokota O, Tsuchiya K, Arai T, Yagishita S, Matsubara O, Mochizuki A et al (2009) Clinicopathological characterization of Pick\u2019s disease versus frontotemporal lobar degeneration with ubiquitin\/TDP-43-positive inclusions. Acta Neuropathol 117:429\u2013444. https:\/\/doi.org\/10.1007\/s00401-009-0493-4","journal-title":"Acta Neuropathol"},{"key":"2899_CR55","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1007\/s00401-007-0329-z","volume":"115","author":"O Yokota","year":"2008","unstructured":"Yokota O, Tsuchiya K, Terada S, Ishizu H, Uchikado H, Ikeda M et al (2008) Basophilic inclusion body disease and neuronal intermediate filament inclusion disease: a comparative clinicopathological study. Acta Neuropathol 115:561\u2013575. https:\/\/doi.org\/10.1007\/s00401-007-0329-z","journal-title":"Acta Neuropathol"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02899-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-025-02899-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02899-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:22:20Z","timestamp":1755069740000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-025-02899-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2899"],"URL":"https:\/\/doi.org\/10.1007\/s00401-025-02899-y","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"assertion":[{"value":"23 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 August 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no potential conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was conducted in accordance with the Ethical Guidelines for Human Genome\/Gene Analysis Research and the Guidelines for Medical and Health Research Involving Human Subjects, as set forth by the Japanese government. The use of human biological samples was approved by the Ethics Review committees of Okayama University, the National Hospital Organisation Minami-Okayama Medical Centre, Zikei Hospital, and the Tokyo Metropolitan Institute of Medical Science. Written informed consent was obtained from the family members of the deceased.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"19"}}