芳樟醇调控Nrf2-ARE通路抗神经退行性疾病的作用机制研究进展

Mechanistic Insights into Linalool-Mediated Neuroprotection via Nrf2-ARE Pathway Modulation in Neurodegenerative Diseases

中文关键词:芳樟醇  Nrf2-ARE信号通路  神经退行性疾病  氧化应激  分子机制

keywords:linalool  Nrf2-ARE signaling pathway  neurodegenerative diseases  oxidative stress  molecular mechanism

中文摘要:神经退行性疾病（neurodegenerative diseases，NDDs）是一类以神经元进行性丢失、认知及运动功能障碍为特征的复杂疾病，其发病机制与氧化应激、神经炎症、线粒体功能障碍和蛋白质稳态失衡密切相关。核因子E2相关因子2（nuclear factor erythroid 2-related factor 2，Nrf2）-抗氧化反应元件（antioxidant response element，ARE）信号通路是细胞抵御氧化损伤、维持内稳态的核心防御系统，其激活被认为是防治NDDs的重要途径。芳樟醇为一种广泛存在于多种植物精油中的天然单萜类化合物，已有研究表明，其通过调控Nrf2-ARE通路间接或直接发挥抗氧化和抗炎活性，进而在NDDs中发挥保护作用。该文综述了Nrf2-ARE通路的结构、激活机制及上游调控信号，阐述了芳樟醇通过激活Nrf2-ARE通路调控下游抗氧化酶表达、抑制炎症反应、改善线粒体功能障碍及促进保护性自噬的分子机制，并重点总结了芳樟醇在阿尔茨海默病（Alzheimer's disease，AD）和帕金森病（Parkinson's disease，PD）模型中的保护作用，旨在为阐明芳樟醇抗NDDs的机制及开发Nrf2靶向治疗策略提供新思路。

Abstract:Neurodegenerative diseases (NDDs) are a group of complex disorders characterized by progressive neuronal loss and impairments in cognitive and motor functions. Their pathogenesis is closely linked to oxidative stress, neuroinflammation, mitochondrial dysfunction, and proteostasis imbalance. The Nuclear factor erythroid 2-related factor 2 (Nrf2)-Antioxidant response element (ARE) signaling pathway serves as a central defense system that enables cells to counteract oxidative damage and maintain homeostasis. Activation of this pathway is regarded as a promising therapeutic strategy for preventing and treating neurodegenerative diseases. Linalool is a natural monoterpenoid compound widely found in various plant essential oils. Previous studies have shown that linalool exerts indirect or direct antioxidative and anti-inflammatory effects by modulating the Nrf2-ARE pathway, thereby playing a protective role in neurodegenerative diseases. This article reviews the architecture, activation mechanisms, and upstream regulatory signals of the Nrf2-ARE pathway. It elaborates on the molecular mechanisms by which linalool activates the Nrf2-ARE pathway to upregulate downstream antioxidant enzyme expression, inhibit inflammatory responses, improve mitochondrial dysfunction, and promote protective autophagy. The review also highlights the protective effects of linalool in models of Alzheimer's disease (AD) and Parkinson's disease (PD), aiming to provide new insights into elucidating the mechanisms of linalool against neurodegenerative disorders and developing Nrf2-targeted therapeutic strategies.