Jahan Nushrat, Singh Lovedeep, Sharma Jyoti
University Institute of Pharma Sciences, Chandigarh University, Mohali, Punjab, India.
Department of Chemistry, Khalsa College, Amritsar, Punjab, India.
Neuromolecular Med. 2025 Jul 16;27(1):51. doi: 10.1007/s12017-025-08875-9.
Neurodegenerative diseases consist of a group of progressive disorders characterized by the gradual decline in the structure or function of neurons, which ultimately results in neuronal death. The occurrence and societal effects of these disorders have been consistently rising, presenting considerable public health challenges globally. Multiple interconnected pathways, including oxidative stress, neuroinflammation, nitrosative stress, and apoptosis, drive their progression. NOX-induced ROS disrupts neuronal function, impairs mitochondrial activity, and triggers lipid peroxidation, contributing to neuronal death. Activation of the TLR-4/MAPK/NF-κB pathway triggers neuroinflammation and NLRP3 inflammasome activation. This inflammasome-driven inflammation accelerates neuronal injury and death. Moreover, reduced estrogen receptor expression weakens neuronal defenses, impairing synaptic function, thereby worsening neurodegeneration. Neurodegenerative diseases continue to be without a cure, as existing treatments focus on alleviating symptoms and modifying the disease. Due to their intricate and multifactorial pathophysiology, there is a pressing need for agents capable of targeting multiple pathological mechanisms to effectively combat these disorders. Various phytomolecules have shown promise in tackling different neurodegenerative diseases by modulating key molecular targets. Equol (4',7-isoflavandiol) is a metabolite of daidzein, a soy isoflavone present in soybeans and various other plant sources. Equol has shown significant promise in combating neurodegeneration by modulating mediators involved in oxidative stress, neuroinflammation, nitrosative stress, and apoptosis. Key signaling molecules influenced by equol include TLR-4, MAPKs, NLRP3 inflammasome, ROS, and inflammatory mediators, among others. Considering equol's ability to modulate these signaling mediators, this review explores the mechanistic pathways through which equol confers neuroprotection.
神经退行性疾病是一组进行性疾病，其特征是神经元的结构或功能逐渐衰退，最终导致神经元死亡。这些疾病的发生率和社会影响一直在上升，给全球公共卫生带来了巨大挑战。多种相互关联的途径，包括氧化应激、神经炎症、亚硝化应激和细胞凋亡，推动了它们的进展。NOX诱导的ROS破坏神经元功能，损害线粒体活性，并引发脂质过氧化，导致神经元死亡。TLR-4/MAPK/NF-κB途径的激活触发神经炎症和NLRP3炎性小体激活。这种由炎性小体驱动的炎症加速神经元损伤和死亡。此外，雌激素受体表达降低会削弱神经元防御能力，损害突触功能，从而使神经退行性变恶化。神经退行性疾病仍然无法治愈，因为现有的治疗方法侧重于缓解症状和改变疾病。由于其复杂的多因素病理生理学，迫切需要能够针对多种病理机制的药物来有效对抗这些疾病。各种植物分子已显示出通过调节关键分子靶点来治疗不同神经退行性疾病的潜力。雌马酚（4'，7-异黄酮二醇）是大豆苷元的一种代谢产物，大豆苷元是存在于大豆和其他各种植物来源中的一种大豆异黄酮。雌马酚已显示出通过调节参与氧化应激、神经炎症、亚硝化应激和细胞凋亡的介质来对抗神经退行性变的巨大潜力。受雌马酚影响的关键信号分子包括TLR-4、MAPK、NLRP3炎性小体、ROS和炎症介质等。鉴于雌马酚调节这些信号介质的能力，本综述探讨了雌马酚赋予神经保护作用的机制途径。
