{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T02:32:40Z","timestamp":1780626760101,"version":"3.54.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T00:00:00Z","timestamp":1649116800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurochem Res"],"published-print":{"date-parts":[[2022,9]]},"DOI":"10.1007\/s11064-022-03587-z","type":"journal-article","created":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T10:08:35Z","timestamp":1649153315000},"page":"2684-2702","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Antiepileptic Valproic Acid Ameliorates Charcot-Marie-Tooth 2W (CMT2W) Disease-Associated HARS1 Mutation-Induced Inhibition of Neuronal Cell Morphological Differentiation Through c-Jun N-terminal Kinase"],"prefix":"10.1007","volume":"47","author":[{"given":"Shiori","family":"Memezawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanari","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arisa","family":"Ochiai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miku","family":"Fukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sui","family":"Sawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazunori","family":"Sango","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3618-998X","authenticated-orcid":false,"given":"Junji","family":"Yamauchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,5]]},"reference":[{"key":"3587_CR1","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/glia.20386","volume":"54","author":"P Berger","year":"2006","unstructured":"Berger P, Niemann A, Suter U (2006) Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease). Glia 54:243\u2013257","journal-title":"Glia"},{"key":"3587_CR2","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1097\/WCO.0000000000000373","volume":"29","author":"AM Rossor","year":"2016","unstructured":"Rossor AM, Tomaselli PJ, Reilly MM (2016) Recent advances in the genetic neuropathies. Curr Opin Neurol 29:537\u2013548","journal-title":"Curr Opin Neurol"},{"key":"3587_CR3","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1002\/bies.201600052","volume":"3","author":"E Storkebaum","year":"2016","unstructured":"Storkebaum E (2016) Peripheral neuropathy via mutant tRNA synthetases: inhibition of protein translation provides a possible explanation. BioEssays 3:818\u2013829","journal-title":"BioEssays"},{"key":"3587_CR4","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1002\/1873-3468.12962","volume":"592","author":"V Boczonadi","year":"2018","unstructured":"Boczonadi V, Jennings MJ, Horvath R (2018) The role of tRNA synthetases in neurological and neuromuscular disorders. FEBS Lett 592:703\u2013717","journal-title":"FEBS Lett"},{"key":"3587_CR5","doi-asserted-by":"publisher","unstructured":"Fridman V, Saporta MA (2021) Mechanisms and treatments in demyelinating CMT. Neurotherapeutics. https:\/\/doi.org\/10.1007\/s13311-021-01145-z","DOI":"10.1007\/s13311-021-01145-z"},{"key":"3587_CR6","doi-asserted-by":"publisher","first-page":"6755","DOI":"10.3390\/ijms22136755","volume":"22","author":"P Miniou","year":"2021","unstructured":"Miniou P, Fontes M (2021) Therapeutic development in Charcot-Marie Tooth type 1 disease. Int J Mol Sci 22:6755","journal-title":"Int J Mol Sci"},{"key":"3587_CR7","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1002\/humu.22210","volume":"34","author":"A Vester","year":"2013","unstructured":"Vester A, Velez-Ruiz G, McLaughlin HM, Comparative Sequencing Program NISC, Lupski JR, Talbot K, Vance JM, Zuchner S, Roda RH, Fischbeck KH, Biesecker LG, Nicholson G, Beg AA, Antonellis A (2013) A loss-of-function variant in the human histidyl-tRNA synthetase (HARS) gene is neurotoxic in vivo. Hum Mutat 34:191\u2013199","journal-title":"Hum Mutat"},{"key":"3587_CR8","doi-asserted-by":"publisher","first-page":"2161","DOI":"10.1093\/brain\/awv158","volume":"138","author":"D Safka Brozkova","year":"2015","unstructured":"Safka Brozkova D, Deconinck T, Griffin LB, Ferbert A, Haberlova J, Mazanec R, Lassuthova P, Roth C, Pilunthanakul T, Rautenstrauss B, Janecke AR, Zavadakova P, Chrast R, Rivolta C, Zuchner S, Antonellis A, Beg AA, De Jonghe P, Senderek J, Seeman P, Baets J (2015) Loss of function mutations in HARS cause a spectrum of inherited peripheral neuropathies. Brain 138:2161\u20132172","journal-title":"Brain"},{"key":"3587_CR9","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/humu.23380","volume":"39","author":"JA Abbott","year":"2018","unstructured":"Abbott JA, Meyer-Schuman R, Lupo V, Feely S, Mademan I, Oprescu SN, Griffin LB, Alberti MA, Casasnovas C, Aharoni S, Basel-Vanagaite L, Z\u00fcchner S, De Jonghe P, Baets J, Shy ME, Espin\u00f3s C, Demeler B, Antonellis A, Francklyn C (2018) Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy. Hum Mutat 39:415\u2013432","journal-title":"Hum Mutat"},{"key":"3587_CR10","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1002\/acn3.791","volume":"6","author":"B Royer-Bertrand","year":"2019","unstructured":"Royer-Bertrand B, Tsouni P, Mullen P, Campos Xavier B, Mittaz Crettol L, Lobrinus AJ, Ghika J, Baumgartner MR, Rivolta C, Superti-Furga A, Kuntzer T, Francklyn C, Tran C (2019) Peripheral neuropathy and cognitive impairment associated with a novel monoallelic HARS variant. Ann Clin Transl Neurol 6:1072\u20131080","journal-title":"Ann Clin Transl Neurol"},{"key":"3587_CR11","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1002\/humu.24024","volume":"41","author":"D Galatolo","year":"2020","unstructured":"Galatolo D, Kuo ME, Mullen P, Meyer-Schuman R, Doccini S, Battini R, Lieto M, Tessa A, Filla A, Francklyn C, Antonellis A, Santorelli FM (2020) Bi-allelic mutations in HARS1 severely impair histidyl-tRNA synthetase expression and enzymatic activity causing a novel multisystem ataxic syndrome. Hum Mutat 41:1232\u20131237","journal-title":"Hum Mutat"},{"key":"3587_CR12","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1111\/cge.13793","volume":"98","author":"JPD Padilha","year":"2020","unstructured":"Padilha JPD, Brasil CS, Hoefel AML, Winckler PB, Donis KC, Brusius-Facchin AC, Saute J (2020) Diagnostic yield of targeted sequential and massive panel approaches for inherited neuropathies. Clin Genet 98:185\u2013190","journal-title":"Clin Genet"},{"key":"3587_CR13","doi-asserted-by":"publisher","first-page":"67","DOI":"10.3389\/fcell.2019.00067","volume":"7","author":"A Waldron","year":"2019","unstructured":"Waldron A, Wilcox C, Francklyn C, Ebert A (2019) Knock-down of histidyl-tRNA synthetase causes cell cycle arrest and apoptosis of neuronal progenitor cells in vivo. Front Cell Dev Biol 7:67","journal-title":"Front Cell Dev Biol"},{"key":"3587_CR14","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/febs.15538","volume":"288","author":"R Meyer-Schuman","year":"2021","unstructured":"Meyer-Schuman R, Antonellis A (2021) Evidence for a dominant-negative mechanism in HARS1-mediated peripheral neuropathy. FEBS J 288:91\u201394","journal-title":"FEBS J"},{"key":"3587_CR15","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/febs.15449","volume":"288","author":"P Mullen","year":"2021","unstructured":"Mullen P, Abbott JA, Wellman T, Aktar M, Fjeld C, Demeler B, Ebert AM, Francklyn C (2021) Neuropathy-associated histidyl-tRNA synthetase variants attenuate protein synthesis in vitro and disrupt axon outgrowth in developing zebrafish. FEBS J 288:142\u2013159","journal-title":"FEBS J"},{"key":"3587_CR16","doi-asserted-by":"publisher","unstructured":"Nam DE, Park JH, Park CE, Jung NY, Nam SH, Kwon HM, Kim HS, Kim SB, Son WS, Choi BO, Chung KW (2022) Variants of aminoacyl-tRNA synthetase genes in Charcot-Marie-Tooth disease: a Korean cohort study. J Peripher Nerv Syst. https:\/\/doi.org\/10.1111\/jns.12476","DOI":"10.1111\/jns.12476"},{"key":"3587_CR17","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1002\/jnr.22460","volume":"88","author":"J Yamauchi","year":"2010","unstructured":"Yamauchi J, Torii T, Kusakawa S, Sanbe A, Nakamura K, Takashima S, Hamasaki H, Kawaguchi S, Miyamoto Y, Tanoue A (2010) The mood stabilizer valproic acid improves defective neurite formation caused by Charcot-Marie-Tooth disease-associated mutant Rab7 through the JNK signaling pathway. J Neurosci Res 88:3189\u20133197","journal-title":"J Neurosci Res"},{"key":"3587_CR18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neures.2018.09.016","volume":"139","author":"Y Tatsumi","year":"2019","unstructured":"Tatsumi Y, Matsumoto N, Iibe N, Watanabe N, Torii T, Sango K, Homma K, Miyamoto Y, Sakagami H, Yamauchi J (2019) CMT type 2\u00a0N disease-associated AARS mutant inhibits neurite growth that can be reversed by valproic acid. Neurosci Res 139:69\u201378","journal-title":"Neurosci Res"},{"key":"3587_CR19","doi-asserted-by":"publisher","first-page":"3883","DOI":"10.3390\/ijms22083883","volume":"22","author":"LR de Corrales","year":"2021","unstructured":"de Corrales LR, Losada-P\u00e9rez T, Casas-Tint\u00f3 M (2021) JNK pathway in CNS pathologies. Int J Mol Sci 22:3883","journal-title":"Int J Mol Sci"},{"key":"3587_CR20","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1006\/nbdi.2002.0500","volume":"10","author":"MC Ryan","year":"2002","unstructured":"Ryan MC, Shooter EM, Notterpek L (2002) Aggresome formation in neuropathy models based on peripheral myelin protein 22 mutations. Neurobiol Dis 10:109\u2013118","journal-title":"Neurobiol Dis"},{"key":"3587_CR21","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1016\/j.nbd.2004.07.010","volume":"17","author":"N Liu","year":"2004","unstructured":"Liu N, Yamauchi J, Shooter EM (2004) Recessive, but not dominant, mutations in peripheral myelin protein 22 gene show unique patterns of aggregation and intracellular trafficking. Neurobiol Dis 17:300\u2013309","journal-title":"Neurobiol Dis"},{"key":"3587_CR22","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1128\/MCB.00829-08","volume":"29","author":"Y Sha","year":"2009","unstructured":"Sha Y, Pandit L, Zeng S, Eissa NT (2009) A critical role for CHIP in the aggresome pathway. Mol Cell Biol 29:116\u2013128","journal-title":"Mol Cell Biol"},{"key":"3587_CR23","doi-asserted-by":"crossref","unstructured":"Magupalli VG, Negro R, Tian Y, Hauenstein AV, Di Caprio G, Skillern W, Deng Q, Orning P, Alam HB, Maliga Z, Sharif H, Hu JJ, Evavold CL, Kagan JC, Schmidt FI, Fitzgerald KA, Kirchhausen T, Li Y, Wu H (2020) HDAC6 mediates an aggresome-like mechanism for NLRP3 and pyrin inflammasome activation. Science 369:eaas8995","DOI":"10.1126\/science.aas8995"},{"key":"3587_CR24","doi-asserted-by":"publisher","first-page":"5292","DOI":"10.1074\/jbc.REV119.007721","volume":"294","author":"K Musier-Forsyth","year":"2019","unstructured":"Musier-Forsyth K (2019) Aminoacyl-tRNA synthetases and tRNAs in human disease: an introduction to the JBC reviews thematic series. J Biol Chem 294:5292\u20135293","journal-title":"J Biol Chem"},{"key":"3587_CR25","doi-asserted-by":"publisher","first-page":"5321","DOI":"10.1074\/jbc.REV118.002955","volume":"294","author":"N Wei","year":"2019","unstructured":"Wei N, Zhang Q, Yang XL (2019) Neurodegenerative Charcot-Marie-Tooth disease as a case study to decipher novel functions of aminoacyl-tRNA synthetases. J Biol Chem 294:5321\u20135339","journal-title":"J Biol Chem"},{"key":"3587_CR26","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1111\/jnc.15249","volume":"157","author":"H Zhang","year":"2021","unstructured":"Zhang H, Zhou ZW, Sun L (2021) Aminoacyl-tRNA synthetases in Charcot-Marie-Tooth disease: a gain or a loss? J Neurochem 157:351\u2013369","journal-title":"J Neurochem"},{"key":"3587_CR27","doi-asserted-by":"publisher","unstructured":"Okamoto N, Miya F, Tsunoda T, Kanemura Y, Saitoh S, Kato M, Yanagi K, Kaname T, Kosaki K (2021) Four pedigrees with aminoacyl-tRNA synthetase abnormalities. Neurol Sci. https:\/\/doi.org\/10.1007\/s10072-021-05626-z","DOI":"10.1007\/s10072-021-05626-z"},{"key":"3587_CR28","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1016\/j.ajhg.2015.02.012","volume":"96","author":"C Simons","year":"2015","unstructured":"Simons C, Griffin LB, Helman G, Golas G, Pizzino A, Bloom M, Murphy JLP, Crawford J, Evans SH, Topper S, Whitehead MT, Schreiber JM, Chapman KA, Tifft C, Lu KB, Gamper H, Shigematsu M, Taft RJ, Antonellis A, Hou Y-M, Vanderver A (2015) Loss-of-function alanyl-tRNA synthetase mutations cause an autosomal-recessive early-onset epileptic encephalopathy with persistent myelination defect. Am J Hum Genet 96:675\u2013681","journal-title":"Am J Hum Genet"},{"key":"3587_CR29","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1093\/hmg\/ddab123","volume":"30","author":"E Botta","year":"2021","unstructured":"Botta E, Theil AF, Raams A, Caligiuri G, Giachetti S, Bione S, Accadia M, Lombardi A, Smith DEC, Mendes MI, Swagemakers SMA, van der Spek PJ, Salomons GS, Hoeijmakers JHJ, Yesodharan D, Nampoothiri S, Ogi T, Lehmann AR, Orioli D, Vermeulen W (2021) Protein instability associated with AARS1 and MARS1 mutations causes trichothiodystrophy. Hum Mol Genet 30:1711\u20131720","journal-title":"Hum Mol Genet"},{"key":"3587_CR30","first-page":"100705","volume":"20","author":"N Matsumoto","year":"2019","unstructured":"Matsumoto N, Watanabe N, Iibe N, Tatsumi Y, Hattori K, Takeuchi Y, Oizumi H, Ohbuchi K, Torii T, Miyamoto Y, Yamauchi J (2019) Hypomyelinating leukodystrophy-associated mutation of RARS leads it to the lysosome, inhibiting oligodendroglial morphological differentiation. Biochem Biophys Rep 20:100705","journal-title":"Biochem Biophys Rep"},{"key":"3587_CR31","doi-asserted-by":"crossref","unstructured":"Sawaguchi S, Goto M, Kato Y, Tanaka M, Tago K, Oizumi H, Ohbuchi K, Mizoguchi K, Miyamoto Y, Yamauchi J (2021) Hypomyelinating leukodystrophy 15 (HLD15)-associated mutation of EPRS1 leads to its polymeric aggregation in Rab7-positive vesicle structures, inhibiting oligodendroglial cell morphological differentiation. Polymers 13:1074","DOI":"10.3390\/polym13071074"},{"key":"3587_CR32","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1038\/nature15510","volume":"526","author":"W He","year":"2015","unstructured":"He W, Bai G, Zhou H, Wei N, White NM, Lauer J, Liu H, Shi Y, Dumitru CD, Lettieri K, Shubayev V, Jordanova A, Guergueltcheva V, Griffin PR, Burgess RW, Pfaff SL, Yang XL (2015) CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase. Nature 526:710\u2013714","journal-title":"Nature"},{"key":"3587_CR33","doi-asserted-by":"publisher","first-page":"4397","DOI":"10.1093\/hmg\/ddv176","volume":"24","author":"SJ Grice","year":"2015","unstructured":"Grice SJ, Sleigh JN, Motley WW, Liu JL, Burgess RW, Talbot K, Cader MZ (2015) Dominant, toxic gain-of-function mutations in gars lead to non-cell autonomous neuropathology. Hum Mol Genet 24:4397\u20134406","journal-title":"Hum Mol Genet"},{"key":"3587_CR34","doi-asserted-by":"publisher","first-page":"9216","DOI":"10.1038\/s41598-017-10005-w","volume":"7","author":"JN Sleigh","year":"2017","unstructured":"Sleigh JN, G\u00f3mez-Mart\u00edn A, Wei N, Bai G, Yang XL, Schiavo G (2017) Neuropilin 1 sequestration by neuropathogenic mutant glycyl-tRNA synthetase is permissive to vascular homeostasis. Sci Rep 7:9216","journal-title":"Sci Rep"},{"key":"3587_CR35","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1038\/s41467-018-03461-z","volume":"9","author":"Z Mo","year":"2018","unstructured":"Mo Z, Zhao X, Liu H, Hu Q, Chen XQ, Pham J, Wei N, Liu Z, Zhou J, Burgess RW, Pfaff SL, Caskey CT, Wu C, Bai G, Yang XL (2018) Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy. Nat Commun 9:1007","journal-title":"Nat Commun"},{"key":"3587_CR36","doi-asserted-by":"crossref","unstructured":"Takeuchi Y, Tanaka M, Okura N, Fukui Y, Noguchi K, Hayashi Y, Torii T, Ooizumi H, Ohbuchi K, Mizoguchi K, Miyamoto Y, Yamauchi J (2020) Rare neurologic disease-associated mutations of AIMP1 are related with inhibitory neuronal differentiation which is reversed by ibuprofen.Medicines 7:25","DOI":"10.3390\/medicines7050025"},{"key":"3587_CR37","doi-asserted-by":"publisher","first-page":"L369","DOI":"10.1152\/ajplung.00518.2019","volume":"319","author":"DD Lee","year":"2020","unstructured":"Lee DD, Hochstetler A, Sah E, Xu H, Lowe C-H, Santiaguel S, Thornton JL, Pajakowski A, Margaret A, Schwarz MA (2020) Influence of aminoacyl-tRNA synthetase complex-interacting multifunctional protein 1 on epithelial differentiation and organization during lung development. Am J Physiol Lung Cell Mol Physiol 319:L369\u2013L379","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"3587_CR38","doi-asserted-by":"publisher","first-page":"5438","DOI":"10.2174\/1381612820666140205144900","volume":"20","author":"E Giavini","year":"2014","unstructured":"Giavini E, Menegola E (2014) Teratogenic activity of HDAC inhibitors. Curr Pharm Des 20:5438\u20135442","journal-title":"Curr Pharm Des"}],"container-title":["Neurochemical Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-022-03587-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11064-022-03587-z\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11064-022-03587-z.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T05:19:46Z","timestamp":1662700786000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11064-022-03587-z"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,5]]},"references-count":38,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["3587"],"URL":"https:\/\/doi.org\/10.1007\/s11064-022-03587-z","relation":{},"ISSN":["0364-3190","1573-6903"],"issn-type":[{"value":"0364-3190","type":"print"},{"value":"1573-6903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,5]]},"assertion":[{"value":"11 December 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2022","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 March 2022","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 April 2022","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 have declared that no competing interests exist.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}