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A Kv1.3 channel-specific blocker alleviates neurological impairment through inhibiting T-cell activation in experimental autoimmune encephalomyelitis.


ABSTRACT:

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.

SUBMITTER: Yuan XL 

PROVIDER: S-EPMC6490025 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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A Kv1.3 channel-specific blocker alleviates neurological impairment through inhibiting T-cell activation in experimental autoimmune encephalomyelitis.

Yuan Xiao-Lu XL   Zhao Yi-Peng YP   Huang Jie J   Liu Jun-Chen JC   Mao Wen-Qian WQ   Yin Jun J   Peng Bi-Wen BW   Liu Wan-Hong WH   Han Song S   He Xiao-Hua XH  

CNS neuroscience & therapeutics 20180325 10


<h4>Aim</h4>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 cha  ...[more]

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