, 2007), exposing the drastic consequences from chronic exposure to nitric oxide radicals. Nitration induced oligomerization has also been reported for other disease-related proteins. Recently, the effects of peroxynitrite on oligomerization of α-synuclein by formation of covalent dityrosine cross-links has been demonstrated (Souza et al., 2000). In addition, a widespread accumulation of nitrated α-synuclein has found in several neurodegenerative

diseases associated with Lewy bodies (Giasson http://www.selleckchem.com/products/XL184.html et al., 2000). Furthermore, the presence of nitrated tau in AD brains and its peroxynitrite-induced oligomerization has been observed (Horiguchi et al., 2003). Together, our data identify a posttranslational modification of Aβ and characterize its functional implication that provides evidence for a link between the amyloid and neuroinflammatory component of AD. We think that 3NTyr10-Aβ may be a promising target for a course modifying therapy of AD. The application of specific inhibitors of NOS2 may therefore open a new therapeutic avenue in AD. APP/PS1 transgenic animals (#005864, The Jackson Laboratory) (Jankowsky et al., 2001) and NOS2-deficient animals (# 002609, The Jackson Laboratory) (Laubach et al., 1995) were both of the BC57/Bl6 genetic background. L-NIL was given orally in the water either from 2–3-months

or 7–12 months MAPK inhibitor of age (8 mg/kg body weight). L-NIL was replaced maribavir daily. Mice were housed under standard conditions at 22°C and a 12 hr light-dark cycle with free access to food and water. Animal care and handling was performed according to the declaration of Helsinki and approved by the local ethical committees. Learning and memory testing was conducted in an eight arm maze as previously described (Olton, 1987). Briefly, each arm of the maze was 60 cm long and 6 cm wide and extended

from an octagonal central platform 10 cm in diameter. One centimeter deep food cups were placed 2 cm from the end of each arm. Several visual cues were put outside of the maze, and the room was lit dimly. Mice were trained for 3 days. During each training session, the mouse was placed on the center platform and allowed to move freely in the maze to obtain food pellets, which were presented in all eight arms, for 10 min. Starting day 4, the mice were tested once per day for a total of 14 days. During the test sessions, four randomly selected arms were baited with one pellet of food each; the baited arms were kept unchanged throughout the experiment. The mouse was allowed to move until it collected the four pellets or until 10 min passed, whichever occurred first. Parameters evaluated were reentry into baited arms that had been visited during the session (working memory error) and entries into unbaited arms (reference memory error).