title: Pannexin1 as a novel cerebral target in pathogenesis of hepatic encephalopathy.
abstract: Hepatic encephalopathy (HE) represents a nervous system disorder caused due to liver dysfunction. HE is broadly classified as acute/overt and moderate-minimal HE. Since HE syndrome severely affects quality of life of the patients and it may be life threatening, it is important to develop effective therapeutic strategy against HE. Mainly ammonia neurotoxicity is considered accountable for HE. Increased level of ammonia in the brain activates glutamate-NMDA (N-methyl-D-aspartate) receptor (NMDAR) pathway leading to Ca(2+) influx, energy deficit and oxidative stress in the post synaptic neurons. Moreover, NMDAR blockage has been found to be a poor therapeutic option, as this neurotransmitter receptor plays important role in maintaining normal neurophysiology of the brain. Thus, searching new molecular players in HE pathogenesis is of current concern. There is an evolving concept about roles of the trans-membrane channels in the pathogenesis of a number of neurological complications. Pannexin1 (Panx1) is one of them and has been described to be implicated in stroke, epilepsy and ischemia. Importantly, the pathogenesis of these complications relates to some extent with NMDAR over activation. Thus, it is speculated that HE pathogenesis might also involve Panx1. Indeed, some recent observations in the animal models of HE provide support to this argument. Since opening of Panx1 channel is mostly associated with the neuronal dysfunctions, down regulation of this channel could serve as a relevant therapeutic strategy without producing any serious side effects. In the review article an attempt has been made to summarize the current information on implication of Panx1 in the brain disorders and its prospects for being examined as pharmacological target in HE pathogenesis.
authors.affiliation: Biochemistry Section Centre of Advanced Study in Zoology, Banaras Hindu university, Varanasi, 221005, India.
authors.forename: Papia
authors.initials: P
authors.lastname: Mondal
authors.forename: Surendra Kumar
authors.initials: SK
authors.lastname: Trigun
mesh_terms: D000641:Ammonia / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017630:Connexins / Q000037:antagonists & inhibitors*; D004734:Energy Metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006323:Heart Arrest / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D006801:Humans; D022124:Hyperammonemia / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D017114:Liver Failure, Acute / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009422:Nervous System Diseases / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018384:Oxidative Stress; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020521:Stroke / Q000378:metabolism; D014508:Urea / Q000378:metabolism
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C492764:PANX1 protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D018698:Glutamic Acid; D000641:Ammonia; D014508:Urea; D052248:Nitric Oxide Synthase Type I