Institute for Molecular Biosciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
School of Biomedical Sciences, The University of Queensland, St. Lucia, QLD 4072, Australia.
Curr Drug Targets. 2024;25(13):885-908. doi: 10.2174/0113894501323980240815113851.
The global burden of neurological disorders is evident, yet there remains limited efficacious therapeutics for their treatment. There is a growing recognition of the role of inflammation in diseases of the central nervous system (CNS); among the numerous inflammatory mediators involved, prostaglandins play a crucial role. Prostaglandins are small lipid mediators derived from arachidonic acid via multi-enzymatic pathways. The actions of prostaglandins are varied, with each prostaglandin having a specific role in maintaining homeostasis. In the CNS, prostaglandins can have neuroprotective or neurotoxic properties depending on their specific G-protein receptor. These G-protein receptors have varying subfamilies, tissue distribution, and signal transduction cascades. Further studies into the impact of prostaglandins in CNS-based diseases may contribute to the clarification of their actions, hopefully leading to the development of efficacious therapeutic strategies. This review focuses on the roles played by prostaglandins in neural degeneration, with a focus on Alzheimer's Disease, Multiple Sclerosis, and Amyotrophic Lateral Sclerosis in both preclinical and clinical settings. We further discuss current prostaglandin-related agonists and antagonists concerning suggestions for their use as future therapeutics.
神经系统疾病的全球负担显而易见，但针对其治疗的有效疗法仍然有限。人们越来越认识到炎症在中枢神经系统（CNS）疾病中的作用；在涉及的众多炎症介质中，前列腺素起着至关重要的作用。前列腺素是从小分子脂质衍生而来的，通过多酶途径来自花生四烯酸。前列腺素的作用多种多样，每种前列腺素在维持体内平衡方面都有特定的作用。在中枢神经系统中，前列腺素可能具有神经保护或神经毒性特性，具体取决于其特定的 G 蛋白受体。这些 G 蛋白受体具有不同的亚家族、组织分布和信号转导级联。进一步研究前列腺素在基于中枢神经系统的疾病中的作用可能有助于阐明其作用，希望能开发出有效的治疗策略。本综述重点介绍前列腺素在神经退行性变中的作用，重点关注阿尔茨海默病、多发性硬化症和肌萎缩侧索硬化症在临床前和临床环境中的作用。我们进一步讨论了当前与前列腺素相关的激动剂和拮抗剂，以及关于将其用作未来治疗方法的建议。
