{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:48:14Z","timestamp":1785433694708,"version":"3.56.0"},"reference-count":102,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011259","name":"Liaoning Provincial Key R&D Program","doi-asserted-by":"publisher","award":["2024JH2\/102400054"],"award-info":[{"award-number":["2024JH2\/102400054"]}],"id":[{"id":"10.13039\/501100011259","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005047","name":"Natural Science Foundation of Liaoning Province","doi-asserted-by":"crossref","award":["2025-MS-246"],"award-info":[{"award-number":["2025-MS-246"]}],"id":[{"id":"10.13039\/501100005047","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovation and Entrepreneurship Plan of Science and Technology Talent of Dalian","award":["2022RG09"],"award-info":[{"award-number":["2022RG09"]}]},{"DOI":"10.13039\/501100012465","name":"Dalian Medical University","doi-asserted-by":"crossref","award":["xqnky202412"],"award-info":[{"award-number":["xqnky202412"]}],"id":[{"id":"10.13039\/501100012465","id-type":"DOI","asserted-by":"crossref"}]},{"award":["xqnky202412"],"award-info":[{"award-number":["xqnky202412"]}],"id":[{"id":"https:\/\/ror.org\/04c8eg608","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Scorpion venom peptides, with their stable disulfide backbone, compact structural framework, and highly selective regulation of ion channels, have long been regarded as important molecular probes in neuropharmacology. However, recent studies have revealed their potential for regulating oxidative stress, inflammation, and neuroprotection, making them a new research frontier. In this article, we focus on scorpion venom peptides as drugs, constructing an integrated knowledge framework from structural classification to clinical translation. First, scorpion venom peptides are systematically classified based on cysteine arrangement patterns and three-dimensional folding topology, and their structure\u2013activity relationships are summarized. Based on this, the molecular mechanisms by which scorpion venom peptides regulate ion channels are systematically analyzed. We review the emerging pharmacological activities of scorpion venom peptides. Of particular note, the representative molecule SVHRSP has shown multi-target synergistic antioxidant and neuroprotective activity in models of Parkinson\u2019s disease. We also systematically evaluate the application of engineering strategies, including cyclisation modification, nanodelivery, recombinant expression, and AI-assisted optimization, to overcome the translational bottlenecks in the development of scorpion venom peptides. However, it should be noted that most SVHRSP-related findings have been reported by a single research group; independent replication, pharmacokinetic characterization, and human efficacy data are still lacking. Its IND approval permits clinical investigation but does not yet constitute proven therapeutic benefit in patients. By integrating molecular structure, redox regulation mechanisms, and translational medicine perspectives, this review aims at providing a theoretical basis and practical pathways for scorpion venom peptides as precision therapeutic molecules for oxidative stress-related diseases.<\/jats:p>","DOI":"10.3390\/antiox15060747","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T08:22:56Z","timestamp":1781684576000},"page":"747","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Scorpion Venom Peptides: From Structural Scaffolds to Therapeutic Applications\u2014A Focus on Antioxidant Mechanisms and Translational Perspectives"],"prefix":"10.3390","volume":"15","author":[{"given":"Man","family":"Wang","sequence":"first","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4239-040X","authenticated-orcid":false,"given":"Haoqi","family":"Li","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijin","family":"Xu","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhao","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8290-5230","authenticated-orcid":false,"given":"Lili","family":"Chen","sequence":"additional","affiliation":[{"name":"National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian 116044, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6446","DOI":"10.1038\/s41467-025-60051-6","article-title":"Computational exploration of global venoms for antimicrobial discovery with Venomics artificial intelligence","volume":"16","author":"Guan","year":"2025","journal-title":"Nat. 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