1. Academic Validation
  2. Rapamycin combined with MCC950 to treat multiple sclerosis in experimental autoimmune encephalomyelitis

Rapamycin combined with MCC950 to treat multiple sclerosis in experimental autoimmune encephalomyelitis

  • J Cell Biochem. 2019 Apr;120(4):5160-5168. doi: 10.1002/jcb.27792.
Ling Xu 1 2 Cuili Zhang 1 Nan Jiang 3 Dan He 4 Ying Bai 2 Yi Xin 1
Affiliations

Affiliations

  • 1 Department of Biotechnology, Dalian Medical University, Dalian, China.
  • 2 Department of Clinical Laboratory, Xinhua Hospital Affiliated to Dalian University, Dalian, China.
  • 3 Department of Pathology, The First Affiliated Hospital of Dalian Medical University, Dalian, China.
  • 4 Department of Cardiology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Abstract

Multiple sclerosis (MS) is a highly disabling demyelinating disease, which mainly affects young adults and is difficult to cure. Activated microglia may be involved in the process of neuronal cell damage and release inflammatory cytokines to injure neurons. Rapamycin (RAPA), an immunosuppressant, can induce Autophagy in microglia to delay the process of the disease. As an inhibitor of NLRP3, MCC950 (CP-456773) can regulate the activation of inflammasome. An experimental autoimmune encephalomyelitis model, a disease model of MS, was established to detect the role of activated microglia in the dynamic evolution of MS. Our research showed that RAPA and MCC950 could reduce both the clinical symptom and the release of cytokines in immune cells. MCC950 reduced interleukin-1β (IL-1β) production in vivo and enhanced the effect of RAPA. We hypothesized that inflammation and demyelination in the central nervous system can be reduced by inhibiting the immune response mediated by microglia. This study provides theoretical support to the therapeutic evaluation of RAPA and MCC950 to make the mammalian targets of RAPA and NLRP3 the therapeutic targets of MS.

Keywords

MCC950; NLRP3; autophagy; mammalian target of rapamycin (mTOR); multiple sclerosis (MS); rapamycin (RAPA).

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