Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peroxynitrite and hydroxyl radicals are potent initiators of DNA single strand breakage, which is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose)synthetase (PARS). Rapid activation of PARS depletes the intracellular concentration of its substrate, NAD+, slowing the rate of glycolysis, electron transport and ATP formation. This process can result in acute cell dysfunction and cell necrosis. Accordingly, inhibitors of PARS protect against cell death under these conditions. In addition to the direct cytotoxic pathway regulated by DNA injury and PARS activation, PARS also appears to modulate the course of inflammation by regulating the expression of a number of genes, including the gene for intercellular adhesion molecule 1, collagenase and the inducible nitric oxide synthase. The research into the role of PARS in inflammatory conditions is now supported by novel tools, such as novel, potent inhibitors of PARS, and genetically engineered animals lacking the gene for PARS. In vivo data demonstrate that inhibition of PARS protects against various forms of inflammation, including zymosan or endotoxin induced multiple organ failure, arthritis, allergic encephalomyelitis, and diabetic islet cell destruction. Pharmacological inhibition of PARS may be a promising novel approach for the experimental therapy of various forms of inflammation.
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PMID:Role of poly(ADP-ribose)synthetase in inflammation. 968 9

Peroxynitrite formation has been demonstrated during experimental allergic encephalomyelitis (EAE). Furthermore, peroxynitrite has been identified as an activator of poly(ADP-ribose) synthetase (PARS), an enzyme implicated in neurotoxicity. In the current study, we examined the role of PARS activation in the development of EAE. Administration of the PARS inhibitor 5-iodo-6-amino-1,2-benzopyrone (INH2BP) delayed the onset of EAE and reduced the incidence and severity of disease signs. Moreover, drug treatment lowered iNOS activity and decreased cell infiltration in cervical spinal tissues from EAE-sensitized animals. To conclude, the results of the present investigation suggest that PARS activity may contribute to the pathogenesis of EAE.
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PMID:Role of poly(ADP-ribose) synthetase activation in the development of experimental allergic encephalomyelitis. 1143 Oct 7