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

查看全文 作　　者：Huanpeng [1,3,4]Lu;Jinwei [2]Chai;Zijian [1,3,4]Xu;Jiena [2]Wu;Songzhe [1,3,4]He;Hang [2]Liao;Peng [1,3,4]Huang;Xiaowen [5]Huang;Xi [1,3,4]Chen;Haishan [1]Jiang;Shaogang [1,3,4,6]Qu;Xueqing [2]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》索引2024年第45卷第1期,共17页

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

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

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