Inhibition of JNK/dFOXO pathway and caspases rescues neurological impairments in Drosophila Alzheimers disease model. Se Min Bang, Yoon Ki Hong, Soojin Lee, Kyoung Sang Cho. Biological sciences, Kunkok university, Seoul, Seoul, South Korea.

   Amyloid--42 (A42) has been implicated in the pathogenesis of Alzheimers disease (AD). Neuronal A42 expression induces apoptosis and decreases survival and locomotive activity in Drosophila. However, the mechanism by which A42 induces these neuronal impairments is unclear. In this study, we investigated the underlying pathway in theses impairments. JNK activity was increased in A42-expressing brains, and the A42-induced defects were rescued by reducing JNK or caspase activity through genetic modification or pharmacological treatment. In addition, these impairments were restored by Drosophila forkhead box subgroup O (dFOXO) deficiency. These results suggest that the JNK/dFOXO pathway confers a therapeutic potential for AD.