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通过靶向GPR55调节神经炎症和氧化应激——精神疾病治疗的新方法

Modulation of neuroinflammation and oxidative stress by targeting GPR55 - new approaches in the treatment of psychiatric disorders.

作者信息

Apweiler Matthias, Saliba Soraya Wilke, Sun Lu, Streyczek Jana, Normann Claus, Hellwig Sabine, Bräse Stefan, Fiebich Bernd L

机构信息

Neuroimmunology and Neurochemistry Research Group, Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, D-79104, Freiburg, Germany.

Department of Cardiology and Angiology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, D-79106 Freiburg, Germany.

出版信息

Mol Psychiatry. 2024 Dec;29(12):3779-3788. doi: 10.1038/s41380-024-02614-5. Epub 2024 May 25.

Abstract

Pharmacological treatment of psychiatric disorders remains challenging in clinical, pharmacological, and scientific practice. Even if many different substances are established for treating different psychiatric conditions, subgroups of patients show only small or no response to the treatment. The neuroinflammatory hypothesis of the genesis of psychiatric disorders might explain underlying mechanisms in these non-responders. For that reason, recent research focus on neuroinflammatory processes and oxidative stress as possible causes of psychiatric disorders. G-protein coupled receptors (GPCRs) form the biggest superfamily of membrane-bound receptors and are already well known as pharmacological targets in various diseases. The G-protein coupled receptor 55 (GPR55), a receptor considered part of the endocannabinoid system, reveals promising modulation of neuroinflammatory and oxidative processes. Different agonists and antagonists reduce pro-inflammatory cytokine release, enhance the synthesis of anti-inflammatory mediators, and protect cells from oxidative damage. For this reason, GPR55 ligands might be promising compounds in treating subgroups of patients suffering from psychiatric disorders related to neuroinflammation or oxidative stress. New approaches in drug design might lead to new compounds targeting different pathomechanisms of those disorders in just one molecule.

摘要

在临床、药理和科学实践中,精神疾病的药物治疗仍然具有挑战性。即使有许多不同的药物被用于治疗不同的精神疾病,但仍有部分患者亚组对治疗反应甚微或毫无反应。精神疾病发生的神经炎症假说或许可以解释这些无反应者的潜在机制。因此,近期的研究聚焦于神经炎症过程和氧化应激,将其视为精神疾病可能的病因。G蛋白偶联受体(GPCRs)构成了最大的膜结合受体超家族,并且在各种疾病中作为药理学靶点已广为人知。G蛋白偶联受体55(GPR55)是一种被认为属于内源性大麻素系统的受体,它对神经炎症和氧化过程具有显著的调节作用。不同的激动剂和拮抗剂可减少促炎细胞因子的释放,增强抗炎介质的合成,并保护细胞免受氧化损伤。因此,GPR55配体可能是治疗与神经炎症或氧化应激相关的精神疾病患者亚组的有前景的化合物。药物设计的新方法可能会产生仅针对这些疾病不同发病机制的单一分子的新化合物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b58/11609097/2d747abcdf6a/41380_2024_2614_Fig1_HTML.jpg

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