小胶质细胞 α7 nAChR 的抗炎作用及其在神经保护中的作用。
Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection.
机构信息
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, 28006 Madrid, Spain; Instituto de I+D del Medicamento Teófilo Hernando (ITH), Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
Instituto de Investigación Sanitaria, Servicio de Farmacología Clínica, Hospital Universitario de la Princesa, 28006 Madrid, Spain; Instituto de I+D del Medicamento Teófilo Hernando (ITH), Facultad de Medicina, Universidad Autónoma de Madrid, Spain; Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Spain.
出版信息
Biochem Pharmacol. 2015 Oct 15;97(4):463-472. doi: 10.1016/j.bcp.2015.07.032. Epub 2015 Jul 29.
Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system, being expressed in neurons and non-neuronal cells, where they participate in a variety of physiological responses like memory, learning, locomotion, attention, among others. We will focus on the α7 nAChR subtype, which has been implicated in neuroprotection, synaptic plasticity and neuronal survival, and is considered as a potential therapeutic target for several neurological diseases. Oxidative stress and neuroinflammation are currently considered as two of the most important pathological mechanisms common in neurodegenerative diseases such as Alzheimer, Parkinson or Huntington diseases. In this review, we will first analysed the distribution and expression of nAChR in mammalian brain. Then, we focused on the function of the α7 nAChR subtype in neuronal and non-neuronal cells and its role in immune responses (cholinergic anti-inflammatory pathway). Finally, we will revise the anti-inflammatory pathway promoted via α7 nAChR activation that is related to recruitment and activation of Jak2/STAT3 pathway, which on the one hand inhibits NF-κB nuclear translocation, and on the other hand, activates the master regulator of oxidative stress Nrf2/HO-1. This review provides a profound insight into the role of the α7 nAChR subtype in microglia and point out to microglial α7/HO-1 pathway as an anti-inflammatory therapeutic target.
烟碱型乙酰胆碱受体(nAChRs)广泛分布于中枢神经系统,存在于神经元和非神经元细胞中,参与多种生理反应,如记忆、学习、运动、注意力等。我们将重点关注α7 nAChR 亚型,该亚型与神经保护、突触可塑性和神经元存活有关,被认为是几种神经退行性疾病的潜在治疗靶点。氧化应激和神经炎症目前被认为是阿尔茨海默病、帕金森病或亨廷顿病等神经退行性疾病中最重要的两种共同病理机制。在这篇综述中,我们首先分析了 nAChR 在哺乳动物大脑中的分布和表达。然后,我们专注于α7 nAChR 亚型在神经元和非神经元细胞中的功能及其在免疫反应(胆碱能抗炎途径)中的作用。最后,我们将回顾通过α7 nAChR 激活促进的抗炎途径,该途径与 Jak2/STAT3 途径的募集和激活有关,一方面抑制 NF-κB 的核易位,另一方面激活氧化应激的主要调节剂 Nrf2/HO-1。这篇综述深入探讨了α7 nAChR 亚型在小胶质细胞中的作用,并指出小胶质细胞α7/HO-1 途径是一种抗炎治疗靶点。