Pharmacological strategies for the regulation of inducible nitric oxide synthase: neurodegenerative versus neuroprotective mechanisms.

摘要: Inducible nitric oxide synthase (iNOS) is one of three NOS isoforms generating (NO) by the conversion l-arginine to l-citrulline. iNOS has been found be a major contributor initiation/exacerbation central nervous system (CNS) inflammatory/degenerative conditions through production excessive NO which generates reactive nitrogen species (RNSs). Activation and generation come accepted as marker therapeutic target in neuroinflammatory such those observed ischemia, multiple sclerosis (MS), spinal cord injury (SCI), Alzheimer's disease (AD), inherited peroxisomal (e.g. X-linked adrenoleukodystrophy; X-ALD) lysosomal disorders Krabbe's disease). However, with emergence reports on neuroprotective facets NO, prior dogma about being solely detrimental had modified. While RNSs peroxynitrite (ONOO−) have linked lipid peroxidation, neuronal/oligodendrocyte loss, demyelination neurodegenerative diseases, limited GSNO promote vasodilation attenuate vascular under same ischemic conditions. generated from acts second messenger molecular S-nitrosylation shown control important cellular processes regulation expression/activity certain proteins NF-κB. It now believed that environment context produced largely determines actions (good or bad) this molecule. These multi-faceted aspects make interference activity even more complicated since complete ablation rather than protective most conditions. Investigators search modulating pharmacological agents realized need delicate balance so allow physiologically relevant amounts (such required for host defence/neutotransmission/vasodilation, etc.) but at time block repressing levels causing neuronal/tissue damage demyelination, etc.). The past years seen noteworthy increase novel might prove useful achieving aim harnessing good blocking undesirable NO. review provide basic insights into family enzymes special emphasis role CNS, first part. In part review, we will strive an exhaustive compilation prevalent strategies tested modulation production.