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蝎毒素耐热合成肽可保护秀丽隐杆线虫多巴胺神经元免受 6-羟多巴胺的神经毒性。

Scorpion venom heat-resistant synthetic peptide protects dopamine neurons against 6-hydroxydopamine neurotoxicity in C. elegans.

机构信息

Department of Physiology, College of Basic Medical Sciences, Liaoning Provincial Key Laboratory of Cerebral Diseases, China; National-Local Joint Engineering Research Center for Drug-Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, Dalian, Liaoning 116044, China.

Department of Neurology, Affiliated Dalian Friendship Hospital of Dalian Medical University, Dalian, China.

出版信息

Brain Res Bull. 2022 Nov;190:195-203. doi: 10.1016/j.brainresbull.2022.09.022. Epub 2022 Sep 30.

Abstract

Parkinson's disease (PD) is a common neurodegenerative disease. The main pathological feature is the degeneration and loss of dopaminergic neurons in the substantia nigra, which leads to the significant decrease of dopamine content in the striatum. Our recent studies have shown that scorpion venom heat-resistant synthetic peptide (SVHRSP) have protective effects on neuroinflammation. In this study, using C. elegans induced by 6-hydroxydopamine (6-OHDA) as neurodegenerative model, we investigated the effect of SVHRSP on dopaminergic neurons neurotoxicity. Our results implied that SVHRSP treatment could improve the motor capacity in 6-OHDA-induced C. elegans and improve dopaminergic neuron mediated food sensitivity behavior. After SVHRSP treatment, dopaminergic neuron degeneration induced by 6-OHDA was significantly prevented along with a decreased α-synuclein aggregation and restored lipid deposition in C. elegans induced by 6-OHDA. We also observed the reduced levels of reactive oxygen species (ROS) after SVHRSP treatment in model-building C. elegans. In addition, the genes related to apoptosis, oxidative stress, like ctl-1, egl-1and cat-2 in C. elegans induced by 6-OHDA upregulated after treatment with SVHRSP. In conclusion, SVHRSP may impose anti-PD effect through its neuroprotective action on dopaminergic neurons. This study elucidates the effect and related mechanism of SVHRSP on PD and provides evidences for the therapeutic treatment of PD.

摘要

帕金森病(PD)是一种常见的神经退行性疾病。主要的病理特征是黑质中多巴胺能神经元的变性和丧失,导致纹状体中多巴胺含量显著减少。我们最近的研究表明,蝎子毒液耐热合成肽(SVHRSP)对神经炎症具有保护作用。在这项研究中,我们使用 6-羟多巴胺(6-OHDA)诱导的秀丽隐杆线虫作为神经退行性模型,研究了 SVHRSP 对多巴胺能神经元神经毒性的影响。我们的结果表明,SVHRSP 处理可以改善 6-OHDA 诱导的秀丽隐杆线虫的运动能力,并改善多巴胺能神经元介导的食物敏感性行为。SVHRSP 处理后,6-OHDA 诱导的多巴胺能神经元变性得到明显预防,同时减少了α-突触核蛋白聚集,并恢复了 6-OHDA 诱导的秀丽隐杆线虫中的脂质沉积。我们还观察到,SVHRSP 处理后,模型构建的秀丽隐杆线虫中的活性氧(ROS)水平降低。此外,6-OHDA 诱导的秀丽隐杆线虫中的凋亡、氧化应激相关基因,如ctl-1、egl-1 和 cat-2 ,经 SVHRSP 处理后上调。总之,SVHRSP 可能通过对多巴胺能神经元的神经保护作用发挥抗 PD 作用。本研究阐明了 SVHRSP 对 PD 的作用及其相关机制,为 PD 的治疗提供了依据。

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