الفهرس 
A study of the possible neuroprotective effect of diaminohydroxypyrimidine on 3-nitropropionic acid-induced huntington’s disease in rats
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Abstract
Neuroinflammatory status generated by inducible nitric oxide synthase (iNOS) activation in microglia is one of the main mechanisms that contribute to neuronal death in Huntington{u2019}s disease (HD). GTP cyclohydrolase I (GTPCH I) is the rate limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis; the latter is a key factor for iNOS activation.The aim of the study was to investigate the effect of 2, 4-diamino-6-hydroxypyrimidine (DAHP), GTPCH I enzyme inhibitor, against neuronal loss in 3-nitropropinic acid (3-NP) induced-Huntington{u2019}s disease (HD) in rats.Previously, DAHP has been reported to have anti-apoptotic and anti-inflammatory effect on cerebral ischemia and linked this effect to PI3K/Akt signalling. However, the protective role of DAHP against HD has not been elucidated yet. Therefore, the aim was extended to examine the possible neuroprotective mechanisms of DAHP mediated through PI3K/Akt activation and its correlation to Mas receptor (MasR) in 3-NP rat model. Rats received 3-NP (10 mg/kg/day; i.p.) with or without administration of DAHP (0.5 g/kg/day; i.p.) or wortmannin (WM), a PI3K inhibitor, (15 og/kg/day; i.v.) for 14 days. DAHP improved cognitive, memory and motor abnormalities induced by 3-NP, as confirmed by striatal histopathological specimens and immunohistochemical examination of GFAP. Moreover, DAHP treatment inhibited GTPCH I activity, resulting in decreased BH4 levels and iNOS activation. Also, DAHP upregulated the protein expression of survival protein; p85/p55 (pY458/199)-PI3K and pS473-Akt that in turn boosted the activation of striatal neurotrophic factors and receptor; pS133-CREB, BDNF and pY515-TrKB, which positively affect MasR protein expression and improve mitochondrial dysfunction, as indicated by enhancing both SDH and PGC-1Ü level