A dual functional transcriptome-derived Kunitz-like polypeptide from stony coral Porites lutea displays anti-inflammatory and anti-Parkinson's disease effects in vitro and in vivo

作者：Qian Chen, Cong-Shuang Deng, Wan-Ting Wang, Yang Chen, Xiaoshan Huang, Aili Wang, Nan Xu, Yulin He, Kaixun Cao, Guangyi Fan, Guiyi Gong, Simon Ming‐Yuen Lee · 发表于：Water Biology and Security · 年份：2025 · DOI：10.1016/j.watbs.2025.100516 · 被引用次数：1 · 研究领域：Marine Invertebrate Physiology and Ecology、Venomous Animal Envenomation and Studies、Marine Sponges and Natural Products

Marine biota functions as a reservoir harboring highly diverse bioactive proteins and polypeptides for drug development. Although stony corals are renowned for their high productivity and the crucial role of maintaining ecological balance in the marine ecosystem, investigations concerning structural and functional diversity of their proteins and polypeptides are lagging. Herein, we present a comprehensive report on the repertoire of venom-related proteins and peptides from the coral Porites lutea through transcriptome analysis. Furthermore, a novel ∼6 kDa Kunitz-like polypeptide (PlKuz1) was discovered through a homology search, which was then characterized for its sequence and three-dimensional structure. Electrophysiological experiments and molecular docking analysis revealed that PlKuz1 can specifically inhibit the K v 1.3 channel with an IC 50 of approximately 3 μM. In addition, chromogenic assay revealed that PlKuz1 exhibited a robust plasma kallikrein inhibition effect within the concentration range of 1.25–10 μM. In vitro experiments demonstrated that, at 0.3–3 μM, PlKuz1 exerted neuroprotective and anti-inflammatory effects in 6-OHDA-induced PC12 cells and LPS-stimulated BV2 cells, respectively. Moreover, in vivo experimental results indicated that at the same dosage, PlKuz1 mitigated locomotor deficits and protected against dopamine neuronal loss in a 6-OHDA-induced Parkinson's disease model in zebrafish larvae. Additionally, PlKuz1 alleviated LPS-induced production ...