Department of Neurology, the Seventh Clinical College of China Medical University, No. 24 Central Street, Xinfu District, Fushun, Liaoning 113000, China.
Department of Neurology, Shengjing Hospital of China Medical University, No. 36 Sanhao street, Heping District, Shenyang, Liaoning 110000, China.
Biomed Pharmacother. 2024 Jul;176:116811. doi: 10.1016/j.biopha.2024.116811. Epub 2024 May 24.
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
中枢神经系统（CNS）疾病表现出极其复杂的发病机制。目前仍然缺乏实用且有效的治疗方法，严重影响了人类的生活和健康。激活转录因子 4（ATF4）参与多种病理生理过程的调节，包括 CNS 疾病。鉴于 ATF4 广泛参与 CNS 疾病的病理过程，植物源性生物活性化合物（PDBC）靶向 ATF4 的调控可能成为治疗 CNS 疾病的一种可行策略。然而，PDBC 与 ATF4 之间的调节关系尚不完全清楚。在这里，我们旨在全面综述 PDBC 靶向 ATF4 改善 CNS 疾病的研究，为 CNS 疾病的治疗提供新的方向和思路。我们在 PubMed、Embase、Web of Science 和 Google Scholar 数据库中进行了计算机检索，以确定与 PDBC 靶向 ATF4 治疗 CNS 疾病相关的临床前实验。检索时间范围为各数据库建立至 2023 年 12 月。两名评估员使用关键词“ATF4”、“中枢神经系统”、“神经”、“阿尔茨海默病”、“帕金森病”、“中风”、“脊髓损伤”、“胶质母细胞瘤”、“创伤性脑损伤”和“脊髓损伤”进行了搜索。最终共纳入 31 项研究，涵盖了 27 种 PDBC 的评估。综合体内和体外研究的结果，我们观察到这些 PDBC 通过调节 ATF4 来阻止淀粉样纤维（如 Aβ、tau 和 α-synuclein）的沉积。它们调节 ERS，减少炎症因子的释放，恢复线粒体膜的完整性以防止氧化应激，调节突触可塑性，调节自噬，并激活抗凋亡机制。因此，它们在 CNS 疾病中发挥神经保护作用。许多靶向 ATF4 的 PDBC 已显示出促进 CNS 功能恢复的潜力，为治疗这些疾病提供了广阔的前景。然而，未来的研究需要高质量、大规模和全面的临床前和临床研究来进一步验证这种治疗潜力。
