Cath-KP,a novel peptide derived from frog skin,prevents oxidative stress damage in a Parkinson’s disease modelOACSTPCD
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.
Huanpeng Lu;Jinwei Chai;Zijian Xu;Jiena Wu;Songzhe He;Hang Liao;Peng Huang;Xiaowen Huang;Xi Chen;Haishan Jiang;Shaogang Qu;Xueqing Xu
Department of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,ChinaGuangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,ChinaGuangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,ChinaGuangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Dermatology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,ChinaDepartment of Neurology,Nanfang Hospital,Southern Medical University,Guangzhou,Guangdong 510515,China Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence,Guangzhou,Guangdong 510515,China Key Laboratory of Mental Health of the Ministry of Education,Southern Medical University,Guangzhou,Guangdong 510515,China Department of Neurology,Ganzhou Hospital-Nanfang Hospital,Southern Medical University,Ganzhou,Jiangxi 341001,ChinaGuangdong Provincial Key Laboratory of New Drug Screening,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou,Guangdong 510515,China
临床医学
Cath-KPPeptideParkinson’s diseaseOxidative stressNeuroprotection
《Zoological Research》 2024 (1)
P.108-124,17
supported by the National Natural Science Foundation of China(31772476,31911530077 to X.X.,81870991,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.)。
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