Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease model  

作　　者：Huanpeng Lu Jinwei Chai Zijian Xu Jiena Wu Songzhe He Hang Liao Peng Huang Xiaowen Huang Xi Chen Haishan Jiang Shaogang Qu Xueqing Xu 

机构地区：[1]Department of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China [2]Guangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,China [3]Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China [4]Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,China [5]Department of Dermatology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China [6]Department of Neurology,Ganzhou Hospital-Nanfang Hospital,Southern Medical University,Ganzhou,Jiangxi 341001,China

出　　处：《Zoological Research》2024年第1期108-124,共17页动物学研究（英文）

基　　金：supported by the National Natural Science Foundation of China(31772476 and 31911530077 to X.X.,81870991 and U1603281 to S.Q.);Guangdong Basic and Applied Basic Research Foundation(2023A1515010914 to X.X.);Natural Science Foundation of Guangdong Province(2022A1515010352 to S.Q.)。

摘　　要：Parkinson’s disease(PD)is a neurodegenerative condition that results in dyskinesia,with oxidative stress playing a pivotal role in its progression.Antioxidant peptides may thus present therapeutic potential for PD.In this study,a novel cathelicidin peptide(Cath-KP;GCSGRFCNLF NNRRPGRLTLIHRPGGDKRTSTGLIYV)was identified from the skin of the Asiatic painted frog(Kaloula pulchra).Structural analysis using circular dichroism and homology modeling revealed a uniqueαββconformation for Cath-KP.In vitro experiments,including free radical scavenging and ferric-reducing antioxidant analyses,confirmed its antioxidant properties.Using the 1-methyl-4-phenylpyridinium ion(MPP^(+))-induced dopamine cell line and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mice,Cath-KP was found to penetrate cells and reach deep brain tissues,resulting in improved MPP^(+)-induced cell viability and reduced oxidative stress-induced damage by promoting antioxidant enzyme expression and alleviating mitochondrial and intracellular reactive oxygen species accumulation through Sirtuin-1(Sirt1)/Nuclear factor erythroid 2-related factor 2(Nrf2)pathway activation.Both focal adhesion kinase(FAK)and p38 were also identified as regulatory elements.In the MPTP-induced PD mice,Cath-KP administration increased the number of tyrosine hydroxylase(TH)-positive neurons,restored TH content,and ameliorated dyskinesia.To the best of our knowledge,this study is the first to report on a cathelicidin peptide demonstrating potent antioxidant and neuroprotective properties in a PD model by targeting oxidative stress.These findings expand the known functions of cathelicidins,and hold promise for the development of therapeutic agents for PD.

关 键 词：Cath-KP PEPTIDE Parkinson’s disease Oxidative stress Neuroprotection 

分 类 号：R742.5[医药卫生—神经病学与精神病学]