@entity3957 Selectively Inhibits y-Secretase Activity and Decreases Mitochondrial Ab Production in Neurons from APP/ @entity20933 XXXX .

@entity3958 @entity20933 @entity19 @entity18132 @entity8835 @entity19027 @entity195 @entity3957 @entity19035 @entity25243 @entity855 @entity2383
@entity3957 ( @entity3958 ) is now considered to be a gasotransmitter and may be involved in the pathological process of @entity195 ( @entity195 ). A majority of APP is associated with mitochondria and is a substrate for the mitochondrial y-secretase. The mitochondria-associated APP metabolism where APP intracellular domains (AICD) and Ab are generated locally and may contribute to @entity2383 in @entity195 . Here, we aimed to investigate the ability of @entity3958 to mediate APP processing in mitochondria and assessed the possible mechanisms underlying @entity3958 -mediated @entity195 development. We treated neurons from APP/ @entity20933 @entity19 with a range of @entity8835 ( @entity8835 ) concentrations. @entity8835 attenuated APP processing and decreased Ab production in mitochondria. Meanwhile, @entity8835 did not changed @entity19027 and @entity25243 ( @entity25243 ) protein levels, but @entity8835 (30   M) significantly increased the levels of @entity20933 ( @entity20933 ), @entity19035 , and NCT, as well as improved the y-secretase activity, while @entity8835 (50   M) exhibits the opposing effects. Furthermore, the intracellular @entity855 and the @entity18132 activity of APP/ @entity20933 neurons were increased after 30   M @entity8835 treatment, while the ROS level was decreased and the MMP was stabilized. The effect of @entity8835 differs from DAPT (a non-selective y-secretase inhibitor), and it selectively inhibited y-secretase in vitro, without interacting with Notch and modulating its cleavage. The results indicated that @entity8835 decreases Ab accumulation in mitochondria by selectively inhibiting y-secretase. Thus, we provide a mechanistic view of @entity8835 is a potential anti- @entity195 drug candidate and it may decrease Ab deposition in mitochondria by selectively inhibiting y-secretase activity and therefore protecting the mitochondrial function during @entity195 conditions.
