Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain.
Achucarro Basque Center for Neuroscience, Leioa, Spain.
Glia. 2023 Jan;71(1):103-126. doi: 10.1002/glia.24172. Epub 2022 Mar 30.
The discovery of cannabinoid receptors as the primary molecular targets of psychotropic cannabinoid Δ -tetrahydrocannabinol (Δ -THC) in late 1980s paved the way for investigations on the effects of cannabis-based therapeutics in brain pathology. Ever since, a wealth of results obtained from studies on human tissue samples and animal models have highlighted a promising therapeutic potential of cannabinoids and endocannabinoids in a variety of neurological disorders. However, clinical success has been limited and major questions concerning endocannabinoid signaling need to be satisfactorily addressed, particularly with regard to their role as modulators of glial cells in neurodegenerative diseases. Indeed, recent studies have brought into the limelight diverse, often unexpected functions of astrocytes, oligodendrocytes, and microglia in brain injury and disease, thus providing scientific basis for targeting glial cells to treat brain disorders. This Review summarizes the current knowledge on the molecular and cellular hallmarks of endocannabinoid signaling in glial cells and its clinical relevance in neurodegenerative and chronic inflammatory disorders.
二十世纪八十年代末，人们发现大麻素受体是精神活性大麻素 Δ -四氢大麻酚（Δ -THC）的主要分子靶点，这为研究大麻类药物在大脑病理中的作用铺平了道路。从那时起，大量来自人类组织样本和动物模型的研究结果强调了大麻素和内源性大麻素在多种神经退行性疾病中的治疗潜力。然而，临床应用的成功有限，内源性大麻素信号的主要问题需要得到满意的解决，特别是内源性大麻素信号在神经退行性疾病中作为神经胶质细胞调节剂的作用。事实上，最近的研究揭示了星形胶质细胞、少突胶质细胞和小胶质细胞在脑损伤和疾病中的多种不同的、往往是意想不到的功能，从而为靶向神经胶质细胞治疗脑疾病提供了科学依据。这篇综述总结了内源性大麻素信号在神经胶质细胞中的分子和细胞特征及其在神经退行性和慢性炎症性疾病中的临床相关性的最新知识。
