Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson’s disease model
Huanpeng Lu, 南方医科大学南方医院神经内科, 广东 广州 510515, 中国, Jinwei Chai, Zijian Xu, Jiena Wu, Songzhe He, Hang Liao, Peng Huang, Xiaowen Huang, Xi Chen, Haishan Jiang, Shaogang Qu, Xueqing Xu, 南方医科大学药学院广东省新药筛选重点实验室, 广东 广州 510515, 中国, 粤港澳大湾区脑科学与类脑研究中心, 广东 广州 510515, 中国, 南方医科大学精神健康研究教育部重点实验室, 广东 广州 510515, 中国, 南方医科大学南方医院皮肤科, 广东 广州 510515, 中国, 南方医科大学南方医院赣州医院神经内科, 江西 赣州 341001, 中国
Abstract
Parkinson's disease (PD) is a neurodegenerative condition that results in dyskinesia. This movement disorder is commonly influenced by oxidative stress, which suggests that antioxidant peptides may hold potential for PD treatment. In this study, a novel Cathelicidin peptide named Cath-KP (GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of Kaloula pulchra frog. Circular dichroism and homology modeling analyses demonstrated that Cath-KP possesses a unique αββ structure, while in vitro experiments using ABTS and DPPH radical scavenging activities and FRAP analysis confirmed its antioxidant properties. Additionally, experiments utilizing the MPP+-induced dopamine neuron cell line and MPTP-induced PD mice found that Cath-KP can be internalized into cells and delivered to deep brain tissues, resulting in improved cell viability and the prevention of oxidative stress damage by promoting the expression of antioxidant enzymes and alleviating the accumulation of mitochondrial and intracellular ROS through activating Sirt1/Nrf2 pathway. FAK and p38 also play a part in the regulation of it. Ultimately, Cath-KP administration to MPTP-induced PD mice resulted in the restoration of the quantity of tyrosine hydroxylase (TH) - positive neurons and TH contents, and improved dyskinesia as observed in behavioral experiments. To our knowledge, this is the first Cathelicidin to demonstrate potent antioxidant and neuroprotective properties in PD models by targeting oxidative stress. These findings expand the known functions of Cathelicidins and hold promise for the development of therapeutic agents for PD.