A Kv1.3 channel‐specific blocker alleviates neurological impairment through inhibiting T‐cell activation in experimental autoimmune encephalomyelitis. (25th March 2018)

• Record Type: Journal Article
• Authors: Yuan, Xiao‐Lu; Zhao, Yi‐Peng; Huang, Jie; Liu, Jun‐Chen; Mao, Wen‐Qian; Yin, Jun; Peng, Bi‐Wen; Liu, Wan‐Hong; Han, Song; He, Xiao‐Hua
• Is Part Of: CNS neuroscience & therapeutics. Volume 24:Number 10(2018)
• Page Start: 967
• Page End: 977
• Publication Date: 2018-03-25
• Subjects: EAE -- immunomodulation -- Kv1.3 channel -- multiple sclerosis -- neuroprotection; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12848
• Languages: English
• ISSNs: 1755-5930

Abstract

Summary: Aim: Multiple sclerosis (MS) is a neurological autoimmune disorder characterized by mistaken attacks of inflammatory cells against the central nervous system (CNS), resulting in demyelination and axonal damage. Kv1.3 channel blockers can inhibit T‐cell activation and have been designed for MS therapy. However, little is known about the effects of Kv1.3 blockers on protecting myelin sheaths/axons in MS. This study aimed at investigating the neuroprotection efficacy of a selective Kv1.3 channel blocker ImKTx88 (ImK) in MS animal model. Methods: Experimental autoimmune encephalomyelitis (EAE) rat model was established. The neuroprotective effect of ImK was assessed by immunohistochemistry and transmission electron microscopy (TEM). In addition, the antiinflammatory effect of ImK by suppressing T‐cell activation was assessed by flow cytometry and ELISA in vitro. Results: Our results demonstrated that ImK administration ameliorated EAE clinical severity. Moreover, ImK increased oligodendrocytes survival, preserved axons, and myelin integrity and reduced the infiltration of activated T cells into the CNS. This protective effect of the peptide may be related to its suppression of autoantigen‐specific T‐cell activation via calcium influx inhibition. Conclusion: ImK prevents neurological damage by suppressing T‐cell activation, suggesting the applicability of this peptide in MS therapy.