SIRT1 and neurodegenerative disease: It is noted that in addition to the extracellular signals induced by the insulin and IGF, FOXO activities are also regulated by other exogenous factors such as BDNF and glutamate, as well as intracellular molecules such as AMPK, sirtuin-1 (Sirt1), and JNK, which play roles in neurodegenerative diseases.