title: Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection.
abstract: 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.
authors.affiliation: 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. Electronic address: javier.egea@uam.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Egea
authors.affiliation: 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.
authors.forename: Izaskun
authors.initials: I
authors.lastname: Buendia
authors.affiliation: 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.
authors.forename: Esther
authors.initials: E
authors.lastname: Parada
authors.affiliation: 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.
authors.forename: Elisa
authors.initials: E
authors.lastname: Navarro
authors.affiliation: 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.
authors.forename: Rafael
authors.initials: R
authors.lastname: León
authors.affiliation: 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.
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Lopez
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D007249:Inflammation / Q000378:metabolism; D017628:Microglia / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000235:genetics / Q000378:metabolism*
chemical_list: D064569:alpha7 Nicotinic Acetylcholine Receptor
keywords: Alpha7 nAChR; HO-1; Inflammation; Jak2; Neuroprotection