Neurodegenerative diseases are characterized by the progressive loss of selectively vulnerable populations of neurons, and many factors are involved in its causes. Neurotoxicity and oxidative stress, are the main related factors. The octapeptide Ile‐Ile‐Ala‐Val‐Glu‐Ala‐Gly‐Cys (IEC) was identified from the microalgae Isochrysis zhanjiangensis and exhibited potential anti‐oxidative stress activity. In this study, the stability of α‐synaptic protein binding to IEC was modeled using molecular dynamics, and the results indicated binding stabilization within 60 ns. Oxidative stress in neurons is the major cause of α‐synaptic protein congestion. Therefore, we next evaluated the protective effects of IEC against oxidative stress and neurotoxicity in 6‐ohdainduced Parkinson’s disease (PD) model SH‐SY5Y cells in vitro. In oxidative stress, IEC appeared to increase the expression of the antioxidant enzymes HO‐1 and GPX through the antioxidant pathway of Nrf2, and molecular docking of IEC with Nrf2 and GPX could generate hydrogen bonds. Regarding apoptosis, IEC protected cells by increasing the Bcl‐2/Bax ratio, inhibiting the caspase cascade, acting on p53, and modulating the Jak2/Stat3 pathway. The results indicated that IEC exerted neuroprotective effects through the inhibition of α‐synaptic protein aggregation and antioxidant activity. Therefore, microalgal peptides have promising applications in the pre‐vention and treatment of neurodegenerative diseases.

中文翻译：

---

微藻八肽 IIAVEAGC 通过调节 Nrf2/HO-1 和 Jak2/Stat3 途径减轻 6-OHDA 诱导的 SH-SY5Y 细胞的氧化应激和神经毒性

神经退行性疾病的特点是选择性易受影响的神经元群体逐渐丧失，其病因涉及许多因素。神经毒性和氧化应激是主要的相关因素。从微藻湛江等鞭金藻中鉴定出八肽 Ile-Ile-Ala-Val-Glu-Ala-Gly-Cys (IEC)，具有潜在的抗氧化应激活性。在这项研究中，使用分子动力学对 α-突触蛋白与 IEC 结合的稳定性进行了建模，结果表明在 60 ns 内结合稳定。神经元的氧化应激是α突触蛋白充血的主要原因。因此，我们接下来在体外评估了 IEC 对 6-ohda 诱导的帕金森病 (PD) 模型 SH-SY5Y 细胞氧化应激和神经毒性的保护作用。在氧化应激中，IEC似乎通过Nrf2的抗氧化途径增加抗氧化酶HO-1和GPX的表达，并且IEC与Nrf2和GPX的分子对接可以产生氢键。关于细胞凋亡，IEC通过增加Bcl-2/Bax比率、抑制caspase级联、作用于p53和调节Jak2/Stat3通路来保护细胞。结果表明，IEC通过抑制α突触蛋白聚集和抗氧化活性发挥神经保护作用。因此，微藻肽在神经退行性疾病的预防和治疗中具有广阔的应用前景。