Scientific reports, 2021-07, Vol.11 (1), p.14466-16, Article 14466
2021
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- Autor(en) / Beteiligte
- Titel
- CKD-506: A novel HDAC6-selective inhibitor that exerts therapeutic effects in a rodent model of multiple sclerosis
- Ist Teil von
- Scientific reports, 2021-07, Vol.11 (1), p.14466-16, Article 14466
- Ort / Verlag
- London: Nature Publishing Group UK
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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-γ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-021-93232-6Titel-ID: cdi_doaj_primary_oai_doaj_org_article_5f77b10b118742ed8e9fb83f53cbdc9f
- Format
- –
- Schlagworte
- 631/154/436, 631/154/51, 631/250/371, 631/250/38, Animals, Antidepressive Agents - administration & dosage, Antidepressive Agents - pharmacology, Autoimmune diseases, Blood-brain barrier, Blood-Brain Barrier - drug effects, CD11b antigen, CD4 antigen, CD45 antigen, Cell Proliferation - drug effects, Cytokines - metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Encephalitis, Encephalomyelitis, Autoimmune, Experimental - chemically induced, Encephalomyelitis, Autoimmune, Experimental - drug therapy, Encephalomyelitis, Autoimmune, Experimental - etiology, Experimental allergic encephalomyelitis, Female, Fingolimod Hydrochloride - pharmacology, Histone Deacetylase 6 - antagonists & inhibitors, Histone Deacetylase Inhibitors - administration & dosage, Histone Deacetylase Inhibitors - pharmacology, Humanities and Social Sciences, Inflammation, Lymphocytes T, Macrophages, Macrophages - drug effects, Macrophages - pathology, Mice, Mice, Inbred C57BL, Microglia, multidisciplinary, Multiple sclerosis, Multiple Sclerosis - drug therapy, Multiple Sclerosis - etiology, Myelin, Myelin-Oligodendrocyte Glycoprotein - toxicity, Science, Science (multidisciplinary), Spinal cord, Spinal Cord - drug effects, Spinal Cord - physiopathology, Splenocytes, T-Lymphocytes - drug effects, T-Lymphocytes - pathology, γ-Interferon