Oxidative stress (OS) plays a critical role in the pathophysiology of several brain-related disorders, including neurodegenerative diseases and ischemic stroke, which are the major causes of dementia. The Nrf2-ARE (nuclear factor erythroid 2-related factor 2/antioxidant responsive element antioxidant) system, the primary cellular defense against OS, plays an essential role in neuroprotection by regulating the expressions of antioxidant molecules and enzymes. However, simultaneous events resulting in the overproduction of reactive oxygen species (ROS) and deregulation of the Nrf2-ARE system damage essential cell components and cause loss of neuron structural and functional integrity. On the other hand, TrkB (tropomyosin-related kinase B) signaling, a classical neurotrophin signaling pathway, regulates neuronal survival and synaptic plasticity, which play pivotal roles in memory and cognition. Also, TrkB signaling, specifically the TrkB/PI3K/Akt (TrkB/phosphatidylinositol 3 kinase/protein kinase B) pathway promotes the activation and nuclear translocation of Nrf2, and thus, confers neuroprotection against OS. However, the TrkB signaling pathway is also known to be downregulated in brain disorders due to lack of neurotrophin support. Therefore, activations of TrkB and the Nrf2-ARE signaling system offer a potential approach to the design of novel therapeutic agents for brain disorders. Here, we briefly overview the development of OS and the association between OS and the pathogenesis of neurodegenerative diseases and brain injury. We propose the cellular antioxidant defense and TrkB signaling-mediated cell survival systems be considered pharmacological targets for the treatment of neurodegenerative diseases, and review the literature on the neuroprotective effects of phytochemicals that can co-activate these neuronal defense systems.

氧化应激（OS）在多种大脑相关疾病的病理生理学中起着至关重要的作用，包括神经退行性疾病和缺血性中风，它们是痴呆的主要原因。Nrf2-ARE（核因子红细胞 2 相关因子 2/抗氧化反应元件抗氧化剂）系统是针对 OS 的主要细胞防御，通过调节抗氧化剂分子和酶的表达在神经保护中发挥重要作用。然而，导致活性氧 (ROS) 过量产生和 Nrf2-ARE 系统失调的同时发生的事件会损害重要的细胞成分，并导致神经元结构和功能完整性的丧失。另一方面，TrkB（原肌球蛋白相关激酶 B）信号传导是一种经典的神经营养蛋白信号传导途径，调节神经元存活和突触可塑性，在记忆和认知中发挥着关键作用。此外，TrkB 信号传导，特别是 TrkB/PI3K/Akt（TrkB/磷脂酰肌醇 3 激酶/蛋白激酶 B）途径可促进 Nrf2 的激活和核转位，从而赋予针对 OS 的神经保护作用。然而，由于缺乏神经营养蛋白的支持，TrkB 信号通路在脑部疾病中也会下调。因此，TrkB 和 Nrf2-ARE 信号系统的激活为设计新型脑部疾病治疗药物提供了一种潜在的方法。在此，我们简要概述OS的发展以及OS与神经退行性疾病和脑损伤发病机制的关系。我们建议将细胞抗氧化防御和 TrkB 信号介导的细胞存活系统视为治疗神经退行性疾病的药理学靶点，并回顾了有关可共同激活这些神经元防御系统的植物化学物质的神经保护作用的文献。