Fernández-Ruiz Javier, Pazos María Ruth, García-Arencibia Moisés, Sagredo Onintza, Ramos José A
Department of Biochemistry and Molecular Biology, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Faculty of Medicine, Complutense University, 28040 Madrid, Spain.
Mol Cell Endocrinol. 2008 Apr 16;286(1-2 Suppl 1):S91-6. doi: 10.1016/j.mce.2008.01.001. Epub 2008 Jan 17.
CB2 receptors, the so-called peripheral cannabinoid receptor type, were first described in the immune system, but they have been recently identified in the brain in healthy conditions and, in particular, after several types of cytotoxic stimuli. Specifically, CB2 receptors were identified in microglial cells, astrocytes and, to a lesser extent, in certain subpopulations of neurons. Given the lack of psychoactivity demonstrated by selective CB2 receptor agonists, this receptor becomes an interesting target for the treatment of neurological diseases, in particular, the case of certain neurodegenerative disorders in which induction/up-regulation of CB2 receptors has been already demonstrated. These disorders include Alzheimer's disease, Huntington's chorea, amyotrophic lateral sclerosis and others. Interestingly, in experimental models of these disorders, the activation of CB2 receptors has been related to a delayed progression of neurodegenerative events, in particular, those related to the toxic influence of microglial cells on neuronal homeostasis. The present article will review the evidence supporting that CB2 receptors might represent a key element in the endogenous response against different types of cytotoxic events, and that this receptor type may be a clinically promising target for the control of brain damage in neurodegenerative disorders.
CB2受体,即所谓的外周型大麻素受体,最初是在免疫系统中被发现的,但最近在健康状态下的大脑中也被识别出来,尤其是在经历几种细胞毒性刺激之后。具体而言,在小胶质细胞、星形胶质细胞中发现了CB2受体,在一定程度上,某些神经元亚群中也有发现。鉴于选择性CB2受体激动剂未表现出精神活性,该受体成为治疗神经疾病的一个有吸引力的靶点,特别是在某些已证实存在CB2受体诱导/上调的神经退行性疾病中。这些疾病包括阿尔茨海默病、亨廷顿舞蹈病、肌萎缩侧索硬化症等。有趣的是,在这些疾病的实验模型中,CB2受体的激活与神经退行性事件的进展延迟有关,特别是那些与小胶质细胞对神经元稳态的毒性影响相关的事件。本文将综述相关证据,这些证据支持CB2受体可能是内源性应对不同类型细胞毒性事件的关键因素,并且这种受体类型可能是控制神经退行性疾病脑损伤的一个具有临床前景的靶点。