{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:28:28Z","timestamp":1791361708847,"version":"4.3.1"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["20-BR-02-08"],"award-info":[{"award-number":["20-BR-02-08"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["20-BR-02-10"],"award-info":[{"award-number":["20-BR-02-10"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2020R1A2C4002366"],"award-info":[{"award-number":["NRF-2020R1A2C4002366"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2019R1F1A1045639"],"award-info":[{"award-number":["NRF-2019R1F1A1045639"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002560","name":"Soonchunhyang University","doi-asserted-by":"publisher","award":["Kiyoung Kim"],"award-info":[{"award-number":["Kiyoung Kim"]}],"id":[{"id":"10.13039\/501100002560","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"DOI":"10.3389\/fcell.2020.581942","type":"journal-article","created":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T05:27:20Z","timestamp":1605590840000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["The Role of HDAC6 in TDP-43-Induced Neurotoxicity and UPS Impairment"],"prefix":"10.3389","volume":"8","author":[{"given":"Shinrye","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Younghwi","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myungjin","family":"Jo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Mi","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mookyung","family":"Cheon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seongsoo","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Ryong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Jun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1038\/nchembio.1563","article-title":"Autophagy induction enhances TDP43 turnover and survival in neuronal ALS models.","volume":"10","author":"Barmada","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1523\/JNEUROSCI.4988-09.2010","article-title":"Cytoplasmic mislocalization of TDP-43 is toxic to neurons and enhanced by a mutation associated with familial amyotrophic lateral sclerosis.","volume":"30","author":"Barmada","year":"2010","journal-title":"J. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.pneurobio.2011.10.001","article-title":"Dysfunction of constitutive and inducible ubiquitin-proteasome system in amyotrophic lateral sclerosis: implication for protein aggregation and immune response.","volume":"97","author":"Bendotti","year":"2012","journal-title":"Prog. Neurobiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.scr.2018.01.019","article-title":"Oxidative stress and altered mitochondrial protein expression in the absence of amyloid-beta and tau pathology in iPSC-derived neurons from sporadic Alzheimer\u2019s disease patients.","volume":"27","author":"Birnbaum","year":"2018","journal-title":"Stem Cell Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"138","DOI":"10.4161\/auto.2.2.2405","article-title":"p62\/SQSTM1: a missing link between protein aggregates and the autophagy machinery.","volume":"2","author":"Bjorkoy","year":"2006","journal-title":"Autophagy"},{"key":"B6","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1369\/jhc.2008.952044","article-title":"Assessment of apoptosis by immunohistochemistry to active caspase-3, active caspase-7, or cleaved PARP in monolayer cells and spheroid and subcutaneous xenografts of human carcinoma.","volume":"57","author":"Bressenot","year":"2009","journal-title":"J. Histochem. Cytochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"867","DOI":"10.2741\/2727","article-title":"Multiple roles of TDP-43 in gene expression, splicing regulation, and human disease.","volume":"13","author":"Buratti","year":"2008","journal-title":"Front. Biosci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3109\/01677063.2015.1077832","article-title":"Rapamycin alleviates pathogenesis of a new Drosophila model of ALS-TDP.","volume":"29","author":"Cheng","year":"2015","journal-title":"J. Neurogenet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.neulet.2018.04.053","article-title":"TDP-43 interacts with mitochondrial proteins critical for mitophagy and mitochondrial dynamics.","volume":"678","author":"Davis","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.freeradbiomed.2011.08.005","article-title":"Assessing bioenergetic function in response to oxidative stress by metabolic profiling.","volume":"51","author":"Dranka","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1621","DOI":"10.1016\/j.neuroscience.2010.06.018","article-title":"Mutant TAR DNA-binding protein-43 induces oxidative injury in motor neuron-like cell.","volume":"169","author":"Duan","year":"2010","journal-title":"Neuroscience"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/nature09320","article-title":"Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS.","volume":"466","author":"Elden","year":"2010","journal-title":"Nature"},{"key":"B13","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1038\/35006074","article-title":"A Drosophila model of Parkinson\u2019s disease.","volume":"404","author":"Feany","year":"2000","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/emboj.2009.324","article-title":"Knockdown of transactive response DNA-binding protein (TDP-43) downregulates histone deacetylase 6.","volume":"29","author":"Fiesel","year":"2010","journal-title":"EMBO J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1016\/j.neurol.2013.06.003","article-title":"Mitochondrial dysfunctions in Parkinson\u2019s disease.","volume":"170","author":"Gautier","year":"2014","journal-title":"Rev. Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"2983","DOI":"10.1093\/brain\/aww224","article-title":"TDP-43 stage, mixed pathologies, and clinical Alzheimer\u2019s-type dementia.","volume":"139","author":"James","year":"2016","journal-title":"Brain"},{"key":"B17","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/S0092-8674(03)00939-5","article-title":"The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress.","volume":"115","author":"Kawaguchi","year":"2003","journal-title":"Cell"},{"key":"B18","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.neurobiolaging.2017.02.016","article-title":"Enhancing Mitofusin\/Marf ameliorates neuromuscular dysfunction in Drosophila models of TDP-43 proteinopathies.","volume":"54","author":"Khalil","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"B19","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/ng.2853","article-title":"Therapeutic modulation of eIF2alpha phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models.","volume":"46","author":"Kim","year":"2014","journal-title":"Nat. Genet."},{"key":"B20","doi-asserted-by":"publisher","first-page":"34097","DOI":"10.1074\/jbc.M110.154831","article-title":"Amyotrophic lateral sclerosis-associated proteins TDP-43 and FUS\/TLS function in a common biochemical complex to co-regulate HDAC6 mRNA.","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1393","DOI":"10.1016\/j.febslet.2009.12.047","article-title":"Mechanisms of cross-talk between the ubiquitin-proteasome and autophagy-lysosome systems.","volume":"584","author":"Korolchuk","year":"2010","journal-title":"FEBS Lett."},{"key":"B22","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/j.molcel.2005.04.021","article-title":"HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor.","volume":"18","author":"Kovacs","year":"2005","journal-title":"Mol. Cell."},{"key":"B23","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/emboj.2009.405","article-title":"HDAC6 controls autophagosome maturation essential for ubiquitin-selective quality-control autophagy.","volume":"29","author":"Lee","year":"2010","journal-title":"EMBO J."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.1080\/15548627.2019.1686729","article-title":"PTK2\/FAK regulates UPS impairment via SQSTM1\/p62 phosphorylation in TARDBP\/TDP-43 proteinopathies.","volume":"16","author":"Lee","year":"2019","journal-title":"Autophagy"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1093\/hmg\/ddy066","article-title":"TDP-43 controls lysosomal pathways thereby determining its own clearance and cytotoxicity.","volume":"27","author":"Leibiger","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-016-0031-z","article-title":"p62 links the autophagy pathway and the ubiqutin-proteasome system upon ubiquitinated protein degradation.","volume":"21","author":"Liu","year":"2016","journal-title":"Cell Mol. Biol. Lett."},{"key":"B27","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18050954","article-title":"Tubacin, an HDAC6 Selective Inhibitor, Reduces the Replication of the Japanese Encephalitis Virus via the Decrease of Viral RNA Synthesis.","volume":"18","author":"Lu","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.brainresbull.2012.09.005","article-title":"Mitochondrial dysfunction in human TDP-43 transfected NSC34 cell lines and the protective effect of dimethoxy curcumin.","volume":"89","author":"Lu","year":"2012","journal-title":"Brain Res. Bull."},{"key":"B30","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s00401-011-0845-8","article-title":"A harmonized classification system for FTLD-TDP pathology.","volume":"122","author":"Mackenzie","year":"2011","journal-title":"Acta Neuropathol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26645","article-title":"TDP-43 Proteinopathy: Aggregation and Propagation in the Pathogenesis of Amyotrophic Lateral Sclerosis.","volume":"31","author":"Meriggioli","year":"2016","journal-title":"Mov. Disord."},{"key":"B32","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.","volume":"314","author":"Neumann","year":"2006","journal-title":"Science"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2018.04.006","article-title":"Autophagy as a common pathway in amyotrophic lateral sclerosis.","volume":"697","author":"Nguyen","year":"2018","journal-title":"Neurosci. Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"3584","DOI":"10.1128\/JVI.69.6.3584-3596.1995","article-title":"Cloning and characterization of a novel cellular protein. TDP-43, that binds to human immunodeficiency virus type 1 TAR DNA sequence motifs.","volume":"69","author":"Ou","year":"1995","journal-title":"J. Virol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1038\/nature05853","article-title":"HDAC6 rescues neurodegeneration and provides an essential link between autophagy and the UPS.","volume":"447","author":"Pandey","year":"2007","journal-title":"Nature"},{"key":"B36","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1007\/s13311-015-0338-x","article-title":"TDP-43 Proteinopathy and ALS: Insights into Disease Mechanisms and Therapeutic Targets.","volume":"12","author":"Scotter","year":"2015","journal-title":"Neurotherapeutics"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1242\/jcs.140087","article-title":"Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species.","volume":"127","author":"Scotter","year":"2014","journal-title":"J. Cell Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"16325","DOI":"10.1073\/pnas.1003459107","article-title":"Altered distributions of Gemini of coiled bodies and mitochondria in motor neurons of TDP-43 transgenic mice.","volume":"107","author":"Shan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B39","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1007\/978-3-319-89689-2_9","article-title":"Mechanisms Associated with TDP-43 Neurotoxicity in ALS\/FTLD.","volume":"20","author":"Shenouda","year":"2018","journal-title":"Adv. Neurobiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.bbadis.2009.08.012","article-title":"Mitochondrial dysfunction in amyotrophic lateral sclerosis.","volume":"1802","author":"Shi","year":"2010","journal-title":"Biochim. Biophys. Acta"},{"key":"B41","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.mcn.2007.03.007","article-title":"TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein.","volume":"35","author":"Strong","year":"2007","journal-title":"Mol. Cell. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1093\/hmg\/ddt028","article-title":"Hdac6 deletion delays disease progression in the SOD1G93A mouse model of ALS.","volume":"22","author":"Taes","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"B43","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1097\/NEN.0b013e31822c62cf","article-title":"Accumulation of transactive response DNA binding protein 43 in mild cognitive impairment and Alzheimer disease.","volume":"70","author":"Tremblay","year":"2011","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"B44","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.bbadis.2014.07.028","article-title":"The interplay between autophagy and the ubiquitin-proteasome system in cardiac proteotoxicity.","volume":"1852","author":"Wang","year":"2015","journal-title":"Biochim. Biophys. Acta"},{"key":"B45","doi-asserted-by":"publisher","first-page":"15024","DOI":"10.1073\/pnas.1206362109","article-title":"Autophagy activators rescue and alleviate pathogenesis of a mouse model with proteinopathies of the TAR DNA-binding protein 43.","volume":"109","author":"Wang","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007947","article-title":"TDP-43 induces mitochondrial damage and activates the mitochondrial unfolded protein response.","volume":"15","author":"Wang","year":"2019","journal-title":"PLoS Genet."},{"key":"B47","doi-asserted-by":"publisher","first-page":"10851","DOI":"10.1523\/JNEUROSCI.1630-10.2010","article-title":"Wild-type human TDP-43 expression causes TDP-43 phosphorylation, mitochondrial aggregation, motor deficits, and early mortality in transgenic mice.","volume":"30","author":"Xu","year":"2010","journal-title":"J. Neurosci."},{"key":"B48","doi-asserted-by":"publisher","first-page":"5310","DOI":"10.1038\/sj.onc.1210599","article-title":"HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention.","volume":"26","author":"Yang","year":"2007","journal-title":"Oncogene"},{"key":"B49","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.molcel.2007.05.033","article-title":"HDAC6 modulates cell motility by altering the acetylation level of cortactin.","volume":"27","author":"Zhang","year":"2007","journal-title":"Mol. Cell."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1168","DOI":"10.1093\/emboj\/cdg115","article-title":"HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo.","volume":"22","author":"Zhang","year":"2003","journal-title":"EMBO J."},{"key":"B51","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.expneurol.2015.07.019","article-title":"TDP-43 activates microglia through NF-kappaB and NLRP3 inflammasome.","volume":"273","author":"Zhao","year":"2015","journal-title":"Exp. Neurol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.581942\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T05:27:23Z","timestamp":1605590843000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2020.581942\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":51,"alternative-id":["10.3389\/fcell.2020.581942"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2020.581942","relation":{},"ISSN":["2296-634X"],"issn-type":[{"value":"2296-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,17]]},"article-number":"581942"}}