title: [Acid-sensing ion channels as a target for neuroprotection: acidotoxicity revisited].
abstract: Protons are widespread in cells and serve a variety of important functions. In certain pathological conditions, acid-base balance was disrupted and therefore excessive protons were generated and accumulated, which is termed acidosis and proved toxic to the organism. In the nervous system, it has been reported that acidosis was a common phenomenon and contributed to neuronal injury in various kinds of neurological diseases, such as ischemic stroke, multiple sclerosis and Huntington's disease. Acid-sensing ion channels (ASICs) is the key receptor of protons and mediates acidosis-induced neuronal injury, but the underlying mechanism remains unclear. Traditionally, Ca(2+) influx through homomeric ASIC1a channels has been considered to be the main cause of acidotoxicity. Recent research showed that extracellular protons trigger a novel form of necroptosis in neurons via ASIC1a-mediated serine/threonine kinase receptor interaction protein 1 (RIP1) activation, independent of ion-conducting function of ASIC1a. In addition, ASIC1a was found in mitochondria and regulated mitochondrial permeability transition-dependent neuronal death. In this article, we will review the recent progresses on the mechanisms underlying ASIC-mediated neuronal death and discuss ASIC modulators involved in this process.
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Medical Sciences, Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Histology and Embryology, Institute of Medical Sciences, Collaborative Innovation Center for Brain Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. xu-happiness@shsmu.edu.cn.
authors.forename: Tian-Le
authors.initials: TL
authors.lastname: Xu
mesh_terms: D062565:Acid Sensing Ion Channels; D000136:Acid-Base Equilibrium; D000138:Acidosis; D016923:Cell Death; D009474:Neurons; D000066829:Neuroprotection
chemical_list: D062565:Acid Sensing Ion Channels