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CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis

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Abstract
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(35-55) (MOG(35-55))-induced experimental autoimmune encephalitis (EAE) under various treatment regimens. CKD-506 exerted prophylactic and therapeutic effects by regulating peripheral immune responses and maintaining blood-brain barrier (BBB) integrity. In MOG(35-55)-re-stimulated splenocytes, CKD-506 decreased proliferation and downregulated the expression of IFN-gamma 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(+) T cells and CD4(-)CD11b(+)CD45(+) 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.
Author(s)
배대권이지영하니나박진솔백지연서동현임희선고수민김태희정다솜손우찬
Issued Date
2021
Type
Article
Keyword
multiple sclerosis (MS)EAECKD506
DOI
10.1038/s41598-021-93232-6
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7461
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_5f77b10b118742ed8e9fb83f53cbdc9f&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,CKD-506:%20A%20novel%20HDAC6-selective%20inhibitor%20that%20exerts%20therapeutic%20effects%20in%20a%20rodent%20model%20of%20multiple%20sclerosis&offset=0&pcAvailability=true
Publisher
SCIENTIFIC REPORTS
Location
미국
Language
한국어
ISSN
2045-2322
Citation Volume
11
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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