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

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

doi:10.24272/j.issn.2095-8137.2023.101

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Huanpeng Lu, Jinwei Chai, Zijian Xu, Jiena Wu, Songzhe He, Hang Liao, Peng Huang, Xiaowen Huang, Xi Chen, Haishan Jiang, Shaogang Qu, Xueqing Xu. Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson’s disease model. Zoological Research, 2024, 45(1): 108-124. doi: 10.24272/j.issn.2095-8137.2023.101

Citation:

Huanpeng Lu, Jinwei Chai, Zijian Xu, Jiena Wu, Songzhe He, Hang Liao, Peng Huang, Xiaowen Huang, Xi Chen, Haishan Jiang, Shaogang Qu, Xueqing Xu. Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson’s disease model. Zoological Research, 2024, 45(1): 108-124. doi: 10.24272/j.issn.2095-8137.2023.101

Citation:

Huanpeng Lu, Jinwei Chai, Zijian Xu, Jiena Wu, Songzhe He, Hang Liao, Peng Huang, Xiaowen Huang, Xi Chen, Haishan Jiang, Shaogang Qu, Xueqing Xu. Cath-KP, a novel peptide derived from frog skin, prevents oxidative stress damage in a Parkinson’s disease model. Zoological Research, 2024, 45(1): 108-124. doi: 10.24272/j.issn.2095-8137.2023.101

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

doi: 10.24272/j.issn.2095-8137.2023.101

Huanpeng Lu^{1, 3, 4, #},
Jinwei Chai^{2, #},
Zijian Xu^{1, 3, 4},
Jiena Wu²,
Songzhe He^{1, 3, 4},
Hang Liao²,
Peng Huang^{1, 3, 4},
Xiaowen Huang⁵,
Xi Chen^{1, 3, 4},
Haishan Jiang¹,
Shaogang Qu^{6, 1, 3, 4
,
,},
Xueqing Xu^{2
,
,}

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

The raw RNA-seq data were deposited in the NCBI Sequence Read Archive (SRA)(BioProjectID PRJNA1021395), GSA Database (Accession No. CRA013484), and Science Data Bank (https://doi.org/10.57760/sciencedb.j00139.00068).
Supplementary data to this article can be found online.
The authors declare that they have no competing interests.
H.L. and J.C. performed the major experiments, organized the data, and wrote the original manuscript. S.Q. and X.X. designed the experiments, supervised the study, evaluated the data, and revised the article. Z.X. performed molecular docking. J.W., S.H., H.L., P.H., and X.C. carried out the experiments. X.H. and H.J. revised the manuscript. All authors read and approved the final version of the manuscript.
#Authors contributed equally to this work

Funds: This work was 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.), and Natural Science Foundation of Guangdong Province (2022A1515010352 to S.Q.)

More Information

Corresponding author: E-mail: sgq9528@smu.edu.cn; Xu2003@smu.edu.cn
Received Date: 2023-05-29
Accepted Date: 2023-06-05

Published Online: 2023-09-12

Abstract

Abstract

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 (Kaloula pulchra). Structural analysis using circular dichroism and homology modeling revealed a unique αββ conformation 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.
- Cath-KP,
- Peptide,
- Parkinson’s disease,
- Oxidative stress,
- Neuroprotection

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References(77)

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