Department of Pathophysiology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Hubei Provincial Key Laboratory of Developmentally Originated Disease, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
CNS Neurosci Ther. 2018 Oct;24(10):967-977. doi: 10.1111/cns.12848. Epub 2018 Mar 25.
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.
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.
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.
ImK prevents neurological damage by suppressing T-cell activation, suggesting the applicability of this peptide in MS therapy.
多发性硬化症（MS）是一种神经自身免疫性疾病，其特征是炎症细胞对中枢神经系统（CNS）的错误攻击，导致脱髓鞘和轴突损伤。Kv1.3 通道阻滞剂可抑制 T 细胞激活，已被设计用于 MS 治疗。然而，对于 Kv1.3 阻滞剂在保护 MS 中髓鞘/轴突方面的作用知之甚少。本研究旨在研究选择性 Kv1.3 通道阻滞剂 ImKTx88（ImK）在 MS 动物模型中的神经保护作用。
建立实验性自身免疫性脑脊髓炎（EAE）大鼠模型。通过免疫组织化学和透射电子显微镜（TEM）评估 ImK 的神经保护作用。此外，通过流式细胞术和 ELISA 在体外评估 ImK 通过抑制 T 细胞激活的抗炎作用。
我们的结果表明，ImK 给药可改善 EAE 临床严重程度。此外，ImK 增加少突胶质细胞的存活，保持轴突和髓鞘的完整性，并减少激活的 T 细胞浸润到中枢神经系统。该肽的这种保护作用可能与其通过抑制钙内流来抑制自身抗原特异性 T 细胞激活有关。
ImK 通过抑制 T 细胞激活来防止神经损伤，表明该肽在 MS 治疗中的适用性。
