| Autor: |
Liu H; School of pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China., Qu D; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China., Cao Y; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.; Nanjing Fenglin Biotechnology Co., 2 Taixi Road, Pukou District, Nanjing 210031, China., Li H; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.; Center for Supramolecular Chemistry and Catalysis, Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Road, Shanghai 200444, China., Wu X; Center for Supramolecular Chemistry and Catalysis, Department of Chemistry, College of Sciences, Shanghai University, 99 Shangda Road, Shanghai 200444, China., Zhu Y; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.; School of Medicine and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China., Tao J; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China., Li Y; School of pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China., Cao C; State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China. |
| Abstrakt: |
Epilepsy is a chronic disease of brain dysfunction, which arises from imbalance between excitatory and inhibitory activities in neural circuits. Previously, we reported that peptide Martentoxin (MarTX), from scorpion Buthus martensii Karsch, displayed antiseizure activities by specifically inhibiting BK(α + β4) channel currents. Injection of MarTX into the hippocampal region of mice significantly alleviated convulsive seizures. However, intravenous injection of MarTX had no antiepileptic efficacy due to the blood-brain barrier (BBB). To address this, here, we designed cell-penetrating peptide TAT-modified MarTX, in which the linker containing three glycines was put between TAT and the N-terminus of MarTX (forming MTX-N-TAT) or between TAT and the C-terminus of MarTX (forming MTX-C-TAT), respectively. We prepared them in a large amount through Escherichia coli overexpression system and then probed their antiseizure activities. Our results indicated that intravenous injection of MTX-C-TAT showed significant therapeutic efficacy of antiseizure. It increased seizure latency, reduced the total seizure duration and the number of seizures at stages 3, 4, and 5, inhibited hippocampal neuronal hyperexcitability, and exhibited neuroprotective effects on hippocampal neurons. These studies implied that MTX-C-TAT displayed intravenous antiseizure activities properly through crossing BBB and would be a potential antiepileptic drug in the future. |
