Lu Jie, Xian Tie-Jun, Li Cheng-Jun, Wang Yang
Department of Respiratory and Critical Care Medicine, The First People's Hospital of Shenyang, Shenyang Brain Hospital, Shenyang, China.
Department of Pleurisy, The Tenth People's Hospital of Shenyang, Shenyang Chest Hospital, Shenyang, China.
Front Aging Neurosci. 2025 Sep 1;17:1671552. doi: 10.3389/fnagi.2025.1671552. eCollection 2025.
Neuroinflammation plays a dual role in the central nervous system, offering protection in acute phases but contributing to chronic damage in neurodegenerative diseases. Estrogen, traditionally recognized for its reproductive functions, exerts extensive neuroprotective effects by modulating neuroinflammatory processes across multiple levels. This review explores the actions of estrogen through its receptors in astrocytes, microglia, and neurons, emphasizing its regulation of signaling pathways such as PI3K/Akt, NF-κB, and WNT/-catenin. Estrogen also enhances mitochondrial function, promotes DNA repair, and interacts with the gut microbiota to influence systemic inflammation. Furthermore, sex-specific responses to 17-estradiol highlight the importance of hormonal context. Together, these findings underscore estrogen's potential as a multifaceted modulator of neuroinflammation and provide insight for precision therapeutic strategies.
神经炎症在中枢神经系统中发挥双重作用，在急性期提供保护，但在神经退行性疾病中导致慢性损伤。雌激素传统上因其生殖功能而被认可，它通过在多个层面调节神经炎症过程发挥广泛的神经保护作用。本综述探讨了雌激素通过其在星形胶质细胞、小胶质细胞和神经元中的受体所起的作用，强调了其对PI3K/Akt、NF-κB和WNT/β-连环蛋白等信号通路的调节。雌激素还增强线粒体功能、促进DNA修复，并与肠道微生物群相互作用以影响全身炎症。此外，对17-β-雌二醇的性别特异性反应突出了激素背景的重要性。这些发现共同强调了雌激素作为神经炎症多方面调节剂的潜力，并为精准治疗策略提供了见解。
