Nitric oxide – mediated signalization and nitrosative stress in neuropathology / Azot oksid – posredovana signalizacija i nitrozativni stres u neuropatologiji

Nitric oxide (NO) is an important signalling molecule in a variety of physiological processes. NO, a gas, is produced from L-arginine by different isoforms of the nitric oxide synthase and serves as mediator in important physiological functions, such as promoting vasodilation of blood vessels and mediating communication between nervous system cells. Contradictory to its physiologic actions, free radical activity of NO can cause cellular damage by the induction of nitrosative stress with significant implications on nervous system diseases. Although the mechanism of NOmediated neurodegeneration still remains unclear, numerous studies suggest its crucial role in modification of protein functions by nitrosylation and nitro-tyrosination. NO contributes to glutamate excitotoxicity, participates in organelle fragmentation, inhibits mitochondrial respiratory complexes and mobilizes zinc from the internal stores. Recently, NO has been emerged as a mediator of epigenetic gene expression and chromatin changes. Besides, NO is a key mediator in the regulation of inflammatory and immune response of the central nervous system. It is involved in down regulation of several aspects of CNS inflammation, but also has a dual role in that it is required for inflammation in some situations. Azot monoksid je va`an signalni molekul u brojnim fiziolo{kim procesima. Ovaj gas se stvara iz L-argi - nina dejstvom tri izoforme azot monoksid sintaze i medijator je va`nih fiziolo{kih funkcija, kao {to su posredovanje u re - gulaciji tonusa krvnih sudova i komunikaciji }elija nervnog sistema. Nasuprot ovim ulogama, kao slobodni radikal, NO mo`e izazvati }elijsko o{te}enje indukcijom nitrozativnog stresa, {to ima zna~ajne implikacije u bolestima nervnog sistema. Mada je mehanizam neurodegeneracije posredovane azot monoksidom jo{ uvek nerazja{njen, brojne studije uka - zu ju na njegovu klju~nu ulogu u modifikaciji funkcije protei - na kroz procese S-nitrozilacije i nitrovanja tirozina. On doprinosi glutamatnoj ekscitotoksi~nosti, u~estvuje u fragmentaciji organela, inhibi{e mitohondrijalne respiratorne komplekse i mobili{e cink iz unutra{njih depoa. Nedavno je ukazano da mo`e biti medijator epigenetske genske ekspresije i promena hromatina. Pored toga, NO je klju~ni posrednik u regulaciji inflamatornog i imunog odgovora CNS. On u~estvuje u nishodnoj regulaciji nekoliko aspekata inflamacije CNS, ali tako|e ispoljava dualisti~ke efekte u uslovima inflamacije.