Abstract

Neurodegenerative disorders are chronic brain diseases that affect humans worldwide. Although many different factors are thought to be involved in the pathogenesis of these disorders, alterations in several key elements such as the ubiquitin–proteasome system (UPS), the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, and the endocannabinoid system (ECS or endocannabinoidome) have been implicated in their etiology. Impairment of these elements has been linked to the origin and progression of neurodegenerative disorders, while their potentiation is thought to promote neuronal survival and overall neuroprotection, as proved with several experimental models. These key neuroprotective pathways can interact and indirectly activate each other. In this review, we summarize the neuroprotective potential of the UPS, ECS, and Nrf2 signaling, both separately and combined, pinpointing their role as a potential therapeutic approach against several hallmarks of neurodegeneration.

Graphical Abstract

中文翻译：

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泛素-蛋白酶体系统、Nrf2 和大麻素组之间的相互作用作为对抗神经退行性变的保护策略：实验证据回顾

摘要

神经退行性疾病是影响全世界人类的慢性脑部疾病。尽管许多不同的因素被认为与这些疾病的发病机制有关，但几个关键要素的改变，如泛素蛋白酶体系统 (UPS)、核因子红细胞 2 相关因子 2 (Nrf2) 信号通路和内源性大麻素系统（ECS 或内源性大麻素组）与其病因有关。这些元素的损伤与神经退行性疾病的起源和进展有关，而它们的增强被认为可以促进神经元存活和整体神经保护，正如几个实验模型所证明的那样。这些关键的神经保护途径可以相互作用并间接相互激活。在这篇综述中，我们总结了 UPS、ECS 和 Nrf2 信号传导的神经保护潜力，无论是单独的还是组合的，明确指出它们作为针对神经退行性疾病的几种特征的潜在治疗方法的作用。

图形概要