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帕金森病模型中斑马鱼中枢神经系统细胞内肽的研究

Study of Intracellular Peptides of the Central Nervous System of Zebrafish () in a Parkinson's Disease Model.

作者信息

Fiametti Louise O, Franco Camilla A, Nunes Leticia O C, de Castro Leandro M, Santos-Filho Norival A

机构信息

Institute of Chemistry, São Paulo State University, Araraquara 14800-060, Brazil.

School of Pharmaceutical Sciences, São Paulo State University, Araraquara 14800-903, Brazil.

出版信息

Int J Mol Sci. 2025 Feb 26;26(5):2017. doi: 10.3390/ijms26052017.

Abstract

Although peptides have been shown to have biological functions in neurodegenerative diseases, their role in Parkinson's disease has been understudied. A previous study by our group, which used a 6-hydroxydopamine zebrafish model, suggested that nine intracellular peptides may play a part in this condition. In this context, our aim is to better understand the role of five of these nine peptides. The selection of peptides was made based on their precursor proteins, which are fatty acid binding protein 7, mitochondrial ribosomal protein S36, MARCKS-related protein 1-B, excitatory amino acid transporter 2 and thymosin beta-4. The peptides were chemically synthesized in solid phase and characterized by high-performance liquid chromatography and mass spectrometry. Circular dichroism was performed to determine the secondary structure of each peptide, which showed that all five peptides maintain a random structure in the aqueous solutions that were studied. Two molecules show a helical profile in trifluoroethanol, a known structuring agent. Cell viability by the MTT assay indicates that all five peptides are not cytotoxic in all concentrations tested in both mouse and human cell lines. Behavioral assay using a 6-OHDA zebrafish larvae model suggest that all peptides help in the recovery of motor function with 24 h treatment at two concentrations. Three peptides showed a complete recovery from the 6-OHDA-induced motor impairment. Further studies are needed to better understand the mechanism of action of these peptides and whether they are truly a potential ally against Parkinson's disease.

摘要

尽管肽已被证明在神经退行性疾病中具有生物学功能,但其在帕金森病中的作用尚未得到充分研究。我们小组之前的一项研究使用6-羟基多巴胺斑马鱼模型,表明九种细胞内肽可能在这种疾病中发挥作用。在此背景下,我们的目标是更好地了解这九种肽中五种的作用。肽的选择基于其前体蛋白,分别是脂肪酸结合蛋白7、线粒体核糖体蛋白S36、MARCKS相关蛋白1-B、兴奋性氨基酸转运体2和胸腺素β-4。这些肽在固相化学合成,并通过高效液相色谱和质谱进行表征。进行圆二色性分析以确定每种肽的二级结构,结果表明所有五种肽在所研究的水溶液中均保持无规结构。在已知的结构剂三氟乙醇中,有两种分子呈现螺旋结构。通过MTT法检测细胞活力表明,在小鼠和人类细胞系中测试的所有浓度下,这五种肽均无细胞毒性。使用6-羟基多巴胺斑马鱼幼虫模型进行的行为分析表明,在两种浓度下处理24小时,所有肽都有助于运动功能的恢复。三种肽显示从6-羟基多巴胺诱导的运动损伤中完全恢复。需要进一步研究以更好地理解这些肽的作用机制,以及它们是否真的是对抗帕金森病的潜在帮手。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d371/11900122/65011d893829/ijms-26-02017-g001.jpg

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