The Role of PGE2 in Age-related Diseases.

IF 2.5 4区医学 Q2 PHARMACOLOGY & PHARMACY

Current drug targets Pub Date : 2025-06-24 DOI:10.2174/0113894501383329250616070727

Jun Guan, Chao Chen, Shanshan Wu, Haihong Zhu

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引用次数: 0

Abstract

In the past several years, human life expectancy has increased dramatically, and the global aging process is accelerating at an unprecedented rate. Impaired organ functions and systemic inflammation increase the risk of aging-related diseases. It seriously affects the quality of life in older adults and places a heavy burden on the global economy and public health. Inflammation is the cornerstone of many age-related diseases, and among various inflammatory mediators, Prostaglandin E2 (PGE2) has emerged as a key player. For example, PGE2 could participate in the progression of Alzheimer's disease (AD) by modulating neuroinflammation. Plasma PGE2 is regarded as a potential and specific diagnostic biomarker, and higher initial PGE2 levels are positively correlated with longer survival in AD. PGE2 also mediates bone and muscle metabolism to affect age-related musculoskeletal diseases, including sarcopenia, osteoporosis, and osteoarthritis. It activates the EP4 receptor on sensory nerves to inhibit sympathetic nerve activity and modulate bone formation. Moreover, the PGE2/EP4 axis positively regulates muscle mass and strength. In diabetes, increased Cox-2 and m-PGES2 promote PGE2 production. The activated PGE2/EP3 axis exacerbates the progression of type 2 diabetes (T2D) by impairing glucose metabolism and accelerating β-cell senescence. Therefore, the role of PGE2 in age-related diseases deserves greater attention. Its involvement is driven by the dysregulation of its biosynthesis, metabolism, and receptor- mediated signaling. Regulating the concentration of PGE2 or modulating receptor activity represents a promising therapeutic strategy for managing age-related diseases.

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PGE2在年龄相关疾病中的作用

在过去的几年里，人类的预期寿命急剧增加，全球老龄化进程正以前所未有的速度加速。器官功能受损和全身炎症会增加患衰老相关疾病的风险。它严重影响老年人的生活质量，给全球经济和公共卫生造成沉重负担。炎症是许多年龄相关疾病的基础，在各种炎症介质中，前列腺素E2 （PGE2）已成为关键角色。例如，PGE2可以通过调节神经炎症参与阿尔茨海默病（AD）的进展。血浆PGE2被认为是一种潜在的特异性诊断生物标志物，较高的初始PGE2水平与AD患者较长的生存期呈正相关。PGE2还介导骨和肌肉代谢，影响与年龄相关的肌肉骨骼疾病，包括肌肉减少症、骨质疏松症和骨关节炎。它激活感觉神经上的EP4受体，抑制交感神经活动，调节骨形成。此外，PGE2/EP4轴正调控肌肉质量和力量。在糖尿病中，Cox-2和m-PGES2的增加促进了PGE2的产生。激活的PGE2/EP3轴通过损害葡萄糖代谢和加速β细胞衰老来加剧2型糖尿病（T2D）的进展。因此，PGE2在年龄相关疾病中的作用值得重视。它的参与是由其生物合成、代谢和受体介导信号的失调所驱动的。调节PGE2浓度或调节受体活性是治疗年龄相关疾病的一种有前景的治疗策略。

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来源期刊

Current drug targets 医学-药学

CiteScore

6.20

自引率

0.00%

发文量

127

审稿时长

3-8 weeks

期刊介绍： Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies. As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.