Huanpeng Lu: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Jinwei Chai: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Zijian Xu: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Jiena Wu: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Songzhe He: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Hang Liao: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Peng Huang: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Xiaowen Huang: Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Xi Chen: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Haishan Jiang: Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
Shaogang Qu: Department of Neurology, Ganzhou Hospital-Nanfang Hospital, Southern Medical University, Ganzhou, Jiangxi 341001, China.
Xueqing Xu: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China. E-mail: Xu2003@smu.edu.cn.
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; GCSGRFCNLFNNRRPGRLTLIHRPGGDKRTSTGLIYV) was identified from the skin of the Asiatic painted frog ( ). Structural analysis using circular dichroism and homology modeling revealed a unique conformation for Cath-KP. 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.
