{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T07:13:03Z","timestamp":1779001983156,"version":"3.51.4"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Despite advances in therapeutic strategies for multiple sclerosis (MS), the therapy options remain limited with various adverse effects. Here, the therapeutic potential of CKD-506, a novel HDAC6-selective inhibitor, against MS was evaluated in mice with myelin oligodendrocyte glycoprotein<jats:sub>35\u201355<\/jats:sub>(MOG<jats:sub>35\u201355<\/jats:sub>)-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood\u2013brain barrier (BBB) integrity. In MOG<jats:sub>35\u201355<\/jats:sub>-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-\u03b3 and IL-17A. CKD-506 downregulated the levels of pro-inflammatory cytokines in the blood of EAE mice. Additionally, CKD-506 decreased the leakage of intravenously administered Evans blue into the spinal cord; CD4<jats:sup>+<\/jats:sup>T cells and CD4<jats:sup>\u2212<\/jats:sup>CD11b<jats:sup>+<\/jats:sup>CD45<jats:sup>+<\/jats:sup>macrophage\/microglia in the spinal cord was also decreased. Moreover, CKD-506 exhibited therapeutic efficacy against MS, even when drug administration was discontinued from day 15 post-EAE induction. Disease exacerbation was not observed when fingolimod was changed to CKD-506 from day 15 post-EAE induction. CKD-506 alleviated depression-like behavior at the pre-symptomatic stage of EAE. In conclusion, CKD-506 exerts therapeutic effects by regulating T cell- and macrophage-mediated peripheral immune responses and strengthening BBB integrity. Our results suggest that CKD-506 is a potential therapeutic agent for MS.<\/jats:p>","DOI":"10.1038\/s41598-021-93232-6","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T10:03:36Z","timestamp":1626257016000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis"],"prefix":"10.1038","volume":"11","author":[{"given":"Daekwon","family":"Bae","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Young","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina","family":"Ha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsol","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyeon","family":"Baek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghyeon","family":"Suh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hee Seon","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soo Min","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taehee","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da","family":"Som Jeong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woo-chan","family":"Son","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"93232_CR1","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/j.1750-3639.2007.00064.x","volume":"17","author":"H Lassmann","year":"2007","unstructured":"Lassmann, H., Bruck, W. & Lucchinetti, C. F. The immunopathology of multiple sclerosis: an overview. Brain Pathol. 17, 210\u2013218 (2007).","journal-title":"Brain Pathol."},{"key":"93232_CR2","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1146\/annurev-immunol-032713-120227","volume":"32","author":"L Steinman","year":"2014","unstructured":"Steinman, L. Immunology of relapse and remission in multiple sclerosis. Annu. Rev. Immunol. 32, 257\u2013281 (2014).","journal-title":"Annu. Rev. Immunol."},{"key":"93232_CR3","doi-asserted-by":"publisher","first-page":"2101","DOI":"10.1007\/s00415-014-7446-0","volume":"261","author":"T Ziemssen","year":"2014","unstructured":"Ziemssen, T. et al. A 2-year observational study of patients with relapsing-remitting multiple sclerosis converting to glatiramer acetate from other disease-modifying therapies: the COPTIMIZE trial. J. Neurol. 261, 2101\u20132111 (2014).","journal-title":"J. Neurol."},{"key":"93232_CR4","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/ana.24747","volume":"80","author":"University of California SFMSET","year":"2016","unstructured":"University of California SFMSET et al. Long-term evolution of multiple sclerosis disability in the treatment era. Ann. Neurol. 80, 499\u2013510 (2016).","journal-title":"Ann. Neurol."},{"key":"93232_CR5","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1038\/nrd3248","volume":"9","author":"V Brinkmann","year":"2010","unstructured":"Brinkmann, V. et al. Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosis. Nat. Rev. Drug Discov. 9, 883\u2013897 (2010).","journal-title":"Nat. Rev. Drug Discov."},{"key":"93232_CR6","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1002\/ana.24286","volume":"76","author":"T Plavina","year":"2014","unstructured":"Plavina, T. et al. Anti-JC virus antibody levels in serum or plasma further define risk of natalizumab-associated progressive multifocal leukoencephalopathy. Ann. Neurol. 76, 802\u2013812 (2014).","journal-title":"Ann. Neurol."},{"key":"93232_CR7","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1080\/13696998.2017.1355310","volume":"2","author":"H Yang","year":"2017","unstructured":"Yang, H. et al. Cost-effectiveness analysis of ocrelizumab versus subcutaneous interferon beta-1a for the treatment of relapsing multiple sclerosis. J. Med. Econ. 2, 1056\u20131065 (2017).","journal-title":"J. Med. Econ."},{"key":"93232_CR8","doi-asserted-by":"publisher","first-page":"8797206","DOI":"10.1155\/2016\/8797206","volume":"2016","author":"EE Hull","year":"2016","unstructured":"Hull, E. E., Montgomery, M. R. & Leyva, K. J. HDAC inhibitors as epigenetic regulators of the immune system: impacts on cancer therapy and inflammatory diseases. Biomed. Res. Int. 2016, 8797206 (2016).","journal-title":"Biomed. Res. Int."},{"key":"93232_CR9","doi-asserted-by":"publisher","first-page":"442","DOI":"10.2119\/molmed.2011.00077","volume":"17","author":"G Faraco","year":"2011","unstructured":"Faraco, G., Cavone, L. & Chiarugi, A. The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis. Mol. Med. 17, 442\u2013447 (2011).","journal-title":"Mol. Med."},{"key":"93232_CR10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.nbd.2017.07.015","volume":"108","author":"A Jayaraman","year":"2017","unstructured":"Jayaraman, A., Soni, A., Prabhakar, B. S., Holterman, M. & Jayaraman, S. The epigenetic drug Trichostatin A ameliorates experimental autoimmune encephalomyelitis via T cell tolerance induction and impaired influx of T cells into the spinal cord. Neurobiol. Dis. 108, 1\u201312 (2017).","journal-title":"Neurobiol. Dis."},{"key":"93232_CR11","doi-asserted-by":"publisher","first-page":"2751","DOI":"10.3390\/ph3092751","volume":"3","author":"S Subramanian","year":"2010","unstructured":"Subramanian, S., Bates, S. E., Wright, J. J., Espinoza-Delgado, I. & Piekarz, R. L. Clinical toxicities of histone deacetylase inhibitors. Pharmaceuticals (Basel) 3, 2751\u20132767 (2010).","journal-title":"Pharmaceuticals (Basel)"},{"key":"93232_CR12","doi-asserted-by":"publisher","first-page":"1688","DOI":"10.1128\/MCB.01154-06","volume":"28","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normally. Mol. Cell. Biol. 28, 1688\u20131701 (2008).","journal-title":"Mol. Cell. Biol."},{"key":"93232_CR13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1111\/febs.12079","volume":"280","author":"Y Li","year":"2013","unstructured":"Li, Y., Shin, D. & Kwon, S. H. Histone deacetylase 6 plays a role as a distinct regulator of diverse cellular processes. FEBS. J. 280, 775\u2013793 (2013).","journal-title":"FEBS. J."},{"key":"93232_CR14","doi-asserted-by":"publisher","first-page":"15704","DOI":"10.1073\/pnas.1313893110","volume":"110","author":"JH Lee","year":"2013","unstructured":"Lee, J. H. et al. Development of a histone deacetylase 6 inhibitor and its biological effects. Proc. Natl. Acad. Sci. USA 110, 15704\u201315709 (2013).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"93232_CR15","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s43440-020-00188-x","volume":"73","author":"D Bae","year":"2020","unstructured":"Bae, D. et al. M-134, a novel HDAC6-selective inhibitor, markedly improved arthritic severity in a rodent model of rheumatoid arthritis when combined with tofacitinib. Pharmacol Rep 73(1), 185\u2013201 (2020).","journal-title":"Pharmacol Rep"},{"key":"93232_CR16","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s13075-017-1357-2","volume":"19","author":"BR Oh","year":"2017","unstructured":"Oh, B. R. et al. Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro. Arthritis Res. Ther. 19, 154 (2017).","journal-title":"Arthritis Res. Ther."},{"key":"93232_CR17","doi-asserted-by":"publisher","first-page":"519","DOI":"10.3389\/fneur.2019.00519","volume":"10","author":"P LoPresti","year":"2019","unstructured":"LoPresti, P. The selective HDAC6 inhibitor ACY-738 impacts memory and disease regulation in an animal model of multiple sclerosis. Front. Neurol. 10, 519 (2019).","journal-title":"Front. Neurol."},{"key":"93232_CR18","doi-asserted-by":"publisher","first-page":"852","DOI":"10.1093\/ibd\/izz317","volume":"26","author":"JW Lee","year":"2020","unstructured":"Lee, J. W. et al. Novel histone deacetylase 6 inhibitor CKD-506 inhibits NF-kappaB signaling in intestinal epithelial cells and macrophages and ameliorates acute and chronic murine colitis. Inflamm. Bowel Dis. 26, 852\u2013862 (2020).","journal-title":"Inflamm. Bowel Dis."},{"key":"93232_CR19","doi-asserted-by":"publisher","first-page":"17297","DOI":"10.1038\/s41598-018-35602-1","volume":"8","author":"EW Choi","year":"2018","unstructured":"Choi, E. W., Song, J. W., Ha, N., Choi, Y. I. & Kim, S. CKD-506, a novel HDAC6-selective inhibitor, improves renal outcomes and survival in a mouse model of systemic lupus erythematosus. Sci. Rep. 8, 17297 (2018).","journal-title":"Sci. Rep."},{"key":"93232_CR20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s13075-020-02258-0","volume":"22","author":"JK Park","year":"2020","unstructured":"Park, J. K. et al. Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis. Arthritis Res. Ther. 22, 176 (2020).","journal-title":"Arthritis Res. Ther."},{"key":"93232_CR21","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1006\/clim.2001.5167","volume":"103","author":"L Izikson","year":"2002","unstructured":"Izikson, L., Klein, R. S., Luster, A. D. & Weiner, H. L. Targeting monocyte recruitment in CNS autoimmune disease. Clin. Immunol. 103, 125\u2013131 (2002).","journal-title":"Clin. Immunol."},{"key":"93232_CR22","doi-asserted-by":"publisher","first-page":"e201800039","DOI":"10.26508\/lsa.201800039","volume":"1","author":"L Sun","year":"2018","unstructured":"Sun, L. et al. Loss of HDAC11 ameliorates clinical symptoms in a multiple sclerosis mouse model. Life. Sci. Alliance. 1, e201800039 (2018).","journal-title":"Life. Sci. Alliance."},{"key":"93232_CR23","doi-asserted-by":"publisher","first-page":"2173","DOI":"10.1152\/jn.00510.2016","volume":"116","author":"D Wang","year":"2016","unstructured":"Wang, D. et al. Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice. J Neurophysiol 116, 2173\u20132179 (2016).","journal-title":"J Neurophysiol"},{"key":"93232_CR24","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/j.jns.2016.11.067","volume":"372","author":"RE Boeschoten","year":"2017","unstructured":"Boeschoten, R. E. et al. Prevalence of depression and anxiety in Multiple Sclerosis: A systematic review and meta-analysis. J. Neurol. Sci. 372, 331\u2013341 (2017).","journal-title":"J. Neurol. Sci."},{"key":"93232_CR25","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.bbi.2013.07.003","volume":"33","author":"S Acharjee","year":"2013","unstructured":"Acharjee, S. Altered cognitive-emotional behavior in early experimental autoimmune encephalitis\u2013cytokine and hormonal correlates. Brain Behav. Immun. 33, 164\u2013172 (2013).","journal-title":"Brain Behav. Immun."},{"issue":"Suppl 2","key":"93232_CR26","doi-asserted-by":"publisher","first-page":"i46","DOI":"10.1136\/annrheumdis-2011-200593","volume":"71","author":"WW Hancock","year":"2012","unstructured":"Hancock, W. W., Akimova, T., Beier, U. H., Liu, Y. & Wang, L. HDAC inhibitor therapy in autoimmunity and transplantation. Ann. Rheum. Dis. 71(Suppl 2), i46-54 (2012).","journal-title":"Ann. Rheum. Dis."},{"key":"93232_CR27","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1172\/JCI69738","volume":"124","author":"AC West","year":"2014","unstructured":"West, A. C. & Johnstone, R. W. New and emerging HDAC inhibitors for cancer treatment. J. Clin. Invest. 124, 30\u201339 (2014).","journal-title":"J. Clin. Invest."},{"key":"93232_CR28","doi-asserted-by":"publisher","first-page":"1228","DOI":"10.1016\/j.jaci.2014.10.002","volume":"135","author":"G Tsuji","year":"2015","unstructured":"Tsuji, G., Okiyama, N., Villarroel, V. A. & Katz, S. I. Histone deacetylase 6 inhibition impairs effector CD8 T-cell functions during skin inflammation. J. Allergy. Clin. Immunol. 135, 1228\u20131239 (2015).","journal-title":"J. Allergy. Clin. Immunol."},{"issue":"6","key":"93232_CR29","doi-asserted-by":"publisher","first-page":"543","DOI":"10.3390\/cells8060543","volume":"8","author":"FK Nally","year":"2019","unstructured":"Nally, F. K., De Santi, C. & McCoy, C. E. Nanomodulation of Macrophages in Multiple Sclerosis. Cells 8(6), 543 (2019).","journal-title":"Cells"},{"key":"93232_CR30","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1001\/archneur.61.10.1613","volume":"61","author":"HL Weiner","year":"2004","unstructured":"Weiner, H. L. Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch. Neurol. 61, 1613\u20131615 (2004).","journal-title":"Arch. Neurol."},{"key":"93232_CR31","doi-asserted-by":"publisher","first-page":"286","DOI":"10.3389\/fphar.2019.00286","volume":"10","author":"J Wang","year":"2019","unstructured":"Wang, J. et al. Targeting microglia and macrophages: a potential treatment strategy for multiple sclerosis. Front. Pharmacol. 10, 286 (2019).","journal-title":"Front. Pharmacol."},{"key":"93232_CR32","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1007\/s11481-015-9614-0","volume":"10","author":"L Legroux","year":"2015","unstructured":"Legroux, L. & Arbour, N. Multiple sclerosis and T lymphocytes: an entangled story. J. Neuroimmune Pharmacol. 10, 528\u2013546 (2015).","journal-title":"J. Neuroimmune Pharmacol."},{"issue":"3","key":"93232_CR33","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.3892\/mmr.2013.1256","volume":"7","author":"AP Kallaur","year":"2013","unstructured":"Kallaur, A. P. et al. Cytokine profile in relapsing-remitting multiple sclerosis patients and the association between progression and activity of the disease. Mol. Med. Rep. 7(3), 1010\u20131020 (2013).","journal-title":"Mol. Med. Rep."},{"issue":"7","key":"93232_CR34","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1007\/s00415-016-8128-x","volume":"263","author":"E Havrdov\u00e1","year":"2016","unstructured":"Havrdov\u00e1, E. et al. Activity of secukinumab, an anti-IL-17A antibody, on brain lesions in RRMS: results from a randomized, proof-of-concept study. J Neurol. 263(7), 1287\u20131295 (2016).","journal-title":"J Neurol."},{"issue":"12","key":"93232_CR35","doi-asserted-by":"publisher","first-page":"4553","DOI":"10.4049\/jimmunol.1700263","volume":"198","author":"CC Lin","year":"2017","unstructured":"Lin, C. C. & Edelson, E. T. New insights into the role of IL-1\u03b2 in EAE and MS. J Immunol. 198(12), 4553\u20134560 (2017).","journal-title":"J Immunol."},{"issue":"10","key":"93232_CR36","doi-asserted-by":"publisher","first-page":"2290","DOI":"10.3390\/cells9102290","volume":"9","author":"D Fresegna","year":"2020","unstructured":"Fresegna, D. et al. Re-Examining the role of TNF in MS pathogenesis and therapy. Cells 9(10), 2290 (2020).","journal-title":"Cells"},{"key":"93232_CR37","doi-asserted-by":"publisher","first-page":"753","DOI":"10.3389\/fimmu.2017.00753","volume":"8","author":"G Arellano","year":"2017","unstructured":"Arellano, G. et al. Th1 and Th17 cells and associated cytokines discriminate among clinically isolated syndrome and multiple sclerosis phenotypes. Front. Immunol. 8, 753 (2017).","journal-title":"Front. Immunol."},{"key":"93232_CR38","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1172\/JCI0215751","volume":"110","author":"B Becher","year":"2002","unstructured":"Becher, B., Durell, B. G. & Noelle, R. J. Experimental autoimmune encephalitis and inflammation in the absence of interleukin-12. J. Clin. Invest. 110, 493\u2013497 (2002).","journal-title":"J. Clin. Invest."},{"issue":"5","key":"93232_CR39","first-page":"277","volume":"7","author":"A Boiko","year":"2001","unstructured":"Boiko, A. et al. Randomized study of antibodies to IFN-g and TNF-a in secondary progressive multiple sclerosis. Clin. Trial Multiple Scler. 7(5), 277\u2013284 (2001).","journal-title":"Clin. Trial Multiple Scler."},{"key":"93232_CR40","first-page":"139","volume":"8","author":"K Saitoh","year":"2016","unstructured":"Saitoh, K. et al. Anti-IL-17A blocking antibody reduces cyclosporin A-induced relapse in experimental autoimmune encephalomyelitis mice. Biochem. Biophys. Rep. 8, 139\u2013145 (2016).","journal-title":"Biochem. Biophys. Rep."},{"issue":"1","key":"93232_CR41","doi-asserted-by":"publisher","first-page":"566","DOI":"10.4049\/jimmunol.177.1.566","volume":"177","author":"Y Komiyama","year":"2006","unstructured":"Komiyama, Y. et al. IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol 177(1), 566\u2013573 (2006).","journal-title":"J Immunol"},{"key":"93232_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejphar.2010.03.043","volume":"636","author":"F Zhang","year":"2010","unstructured":"Zhang, F., Liu, J. & Shi, J. S. Anti-inflammatory activities of resveratrol in the brain: role of resveratrol in microglial activation. Eur. J. Pharmacol. 636, 1\u20137 (2010).","journal-title":"Eur. J. Pharmacol."},{"key":"93232_CR43","doi-asserted-by":"publisher","first-page":"2927","DOI":"10.7150\/thno.25317","volume":"8","author":"B Yan","year":"2018","unstructured":"Yan, B. et al. Histone deacetylase 6 modulates macrophage infiltration during inflammation. Theranostics 8, 2927\u20132938 (2018).","journal-title":"Theranostics"},{"key":"93232_CR44","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.2147\/NDT.S114636","volume":"13","author":"R Brandstadter","year":"2017","unstructured":"Brandstadter, R. & Katz Sand, I. The use of natalizumab for multiple sclerosis. Neuropsychiatr. Dis. Treat. 13, 1691\u20131702 (2017).","journal-title":"Neuropsychiatr. Dis. Treat."},{"key":"93232_CR45","first-page":"261","volume":"12","author":"I Ayzenberg","year":"2016","unstructured":"Ayzenberg, I., Hoepner, R. & Kleiter, I. Fingolimod for multiple sclerosis and emerging indications: appropriate patient selection, safety precautions, and special considerations. Ther. Clin. Risk Manag. 12, 261\u2013272 (2016).","journal-title":"Ther. Clin. Risk Manag."},{"key":"93232_CR46","first-page":"54","volume":"10","author":"MA Lawson","year":"2013","unstructured":"Lawson, M. A., McCusker, R. H. & Kelley, K. W. Interleukin-1 beta converting enzyme is necessary for development of depression-like behavior following intracerebroventricular administration of lipopolysaccharide to mice. J. Neuroinflammation 10, 54 (2013).","journal-title":"J. Neuroinflammation"},{"key":"93232_CR47","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.biopsych.2005.10.013","volume":"59","author":"BB Simen","year":"2006","unstructured":"Simen, B. B., Duman, C. H., Simen, A. A. & Duman, R. S. TNF\u03b1 signaling in depression and anxiety: behavioral consequences of individual receptor targeting. Biol. Psychiatry. 59, 775\u2013785 (2006).","journal-title":"Biol. Psychiatry."},{"key":"93232_CR48","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1038\/s41467-017-00911-y","volume":"8","author":"W Guo","year":"2017","unstructured":"Guo, W. et al. HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients. Nat. Commun. 8, 861 (2017).","journal-title":"Nat. Commun."},{"key":"93232_CR49","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/nm.2396","volume":"17","author":"C d'Ydewalle","year":"2011","unstructured":"d\u2019Ydewalle, C. et al. HDAC6 inhibitors reverse axonal loss in a mouse model of mutant HSPB1-induced Charcot-Marie-Tooth disease. Nat. Med. 17, 968\u2013974 (2011).","journal-title":"Nat. Med."},{"key":"93232_CR50","doi-asserted-by":"publisher","first-page":"3432","DOI":"10.1002\/(SICI)1521-4141(199911)29:11<3432::AID-IMMU3432>3.0.CO;2-2","volume":"29","author":"JA Lyons","year":"1999","unstructured":"Lyons, J. A., San, M., Happ, M. P. & Cross, A. H. B cells are critical to induction of experimental allergic encephalomyelitis by protein but not by a short encephalitogenic peptide. Eur. J. Immunol. 29, 3432\u20133439 (1999).","journal-title":"Eur. J. Immunol."},{"key":"93232_CR51","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1172\/JCI0213595","volume":"109","author":"D Graesser","year":"2002","unstructured":"Graesser, D. et al. Altered vascular permeability and early onset of experimental autoimmune encephalomyelitis in PECAM-1-deficient mice. J. Clin. Invest. 109, 383\u2013392 (2002).","journal-title":"J. Clin. Invest."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93232-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93232-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93232-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T01:18:47Z","timestamp":1699233527000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-93232-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["93232"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-93232-6","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"assertion":[{"value":"29 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"DKB, NH, JSP, JYB, and DHS are employees of CKD Research Institute. The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14466"}}