Many approaches to neurodegenerative diseases that focus on amyloid-β clearance and gene therapy have not been successful. Some therapeutic applications focus on enhancing neuronal cell survival during the pathogenesis of neurodegenerative diseases, including mitochondrial dysfunction. Plasma membrane (PM) redox enzymes are crucial in maintaining cellular physiology and redox homeostasis in response to mitochondrial dysfunction. Neurohormetic phytochemicals are known to induce the expression of detoxifying enzymes under stress conditions. In this study, mechanisms of neuroprotective effects of 4-hydroxycinnamic acid (HCA) were examined by analyzing cell survival, levels of abnormal proteins, and mitochondrial functions in two different neuronal cells. HCA protected two neuronal cells exhibited high expression of PM redox enzymes and the consequent increase in the NAD⁺/NADH ratio. Cells cultured with HCA showed delayed apoptosis and decreased oxidative/nitrative damage accompanied by decreased ROS production in the mitochondria. HCA increased the mitochondrial complexes I and II activities and ATP production. Also, HCA increased mitochondrial fusion and decreased mitochondrial fission. Overall, HCA maintains redox homeostasis and energy metabolism under oxidative/metabolic stress conditions. These findings suggest that HCA could be a promising therapeutic approach for neurodegenerative diseases.

许多专注于淀粉样蛋白-β 清除和基因治疗的神经退行性疾病治疗方法均未取得成功。一些治疗应用侧重于在神经退行性疾病（包括线粒体功能障碍）的发病机制中提高神经元细胞的存活率。质膜 (PM) 氧化还原酶对于维持细胞生理学和响应线粒体功能障碍的氧化还原稳态至关重要。已知神经激素植物化学物质会在压力条件下诱导解毒酶的表达。在这项研究中，通过分析两种不同神经元细胞中的细胞存活、异常蛋白质水平和线粒体功能，研究了 4-羟基肉桂酸 (HCA) 的神经保护作用机制。⁺ /NADH 比率。用 HCA 培养的细胞显示细胞凋亡延迟和氧化/硝化损伤减少，同时线粒体中 ROS 产生减少。HCA 增加了线粒体复合物 I 和 II 的活性以及 ATP 的产生。此外，HCA 增加了线粒体融合并减少了线粒体分裂。总体而言，HCA 在氧化/代谢应激条件下维持氧化还原稳态和能量代谢。这些发现表明 HCA 可能是一种很有前途的神经退行性疾病治疗方法。