Abstract:
Microglia, the innate immune cells of the central nervous system (CNS), execute their sentinel, housekeeping and defense functions through a panoply of genes, receptors and released cytokines, chemokines and neurotrophic factors. Moreover, microglia functions are closely linked to the constant communication with other cell types, among them neurons. Depending on the signaling pathway and type of stimuli involved, the outcome of microglia operation can be neuroprotective or neurodegenerative. Accordingly, microglia are increasingly becoming considered cellular targets for therapeutic intervention. Among signals controlling microglia activity, the endocannabinoid (EC) system has been shown to exert a neuroprotective role in many neurological diseases. Like neurons, microglia express functional EC receptors and can produce and degrade ECs. Interestingly, boosting EC signaling leads to an anti-inflammatory and neuroprotective microglia phenotype. Nonetheless, little evidence is available on the microglia-mediated therapeutic effects of EC compounds. This review focuses on the EC signals acting on the CNS microglia in physiological and pathological conditions, namely on the CB1R, CB2R and TRPV1-mediated regulation of microglia properties. It also provides new evidence, which strengthens the understanding of mechanisms underlying the control of microglia functions by ECs. Given the broad expression of the EC system in glial and neuronal cells, the resulting picture is the need for in vivo studies in transgenic mouse models to dissect the contribution of EC microglia signaling in the neuroprotective effects of EC-derived compounds.
摘要:
小胶质细胞,中枢神经系统(CNS)的先天性免疫细胞,处决他们的哨兵,通过一系列基因的管家和防御功能,受体和释放的细胞因子,趋化因子和神经营养因子。此外,小胶质细胞的功能与与其他细胞类型的持续交流密切相关,其中有神经元。根据所涉及的信号通路和刺激类型,小胶质细胞手术的结果可以是神经保护或神经变性。因此,小胶质细胞越来越成为治疗干预的细胞靶标。在控制小胶质细胞活动的信号中,内源性大麻素(EC)系统已被证明在许多神经系统疾病中发挥神经保护作用。像神经元一样,小胶质细胞表达功能性EC受体,可以产生和降解EC。有趣的是,加强EC信号导致抗炎和神经保护性小胶质细胞表型。尽管如此,关于小胶质细胞介导的EC化合物治疗效果的证据很少.这篇综述集中在生理和病理条件下作用于CNS小胶质细胞的EC信号。即在CB1R上,CB2R和TRPV1介导的小胶质细胞特性调节。它还提供了新的证据,这加强了对ECs控制小胶质细胞功能的潜在机制的理解。鉴于EC系统在神经胶质和神经元细胞中的广泛表达,因此,需要在转基因小鼠模型中进行体内研究,以剖析EC小胶质细胞信号传导在EC衍生化合物的神经保护作用中的作用.