Abstract
Oxidative stress, caused by increased levels of reactive oxidative species (ROS), is considered a major contributor to the aging process. How oxidative stress may bring about changes to structures and function in the aging brain is poorly understood. Oxidative stress activates a number of cellular responses, including activation of the JunβNβterminal kinase (JNK) pathway and autophagy. In addition to their pathological role, ROS also act as signaling molecules. ROS such as nitric oxide have a wellβknown role in learning and memory. In addition, activation of JNK and its transcriptional effector APβ1 are wellβknown mediators of synaptic function and growth. Both are essential mediators of physiological correlates of learning and memory such as longβterm potentiation. JNK and APβ1 are potently activated and regulated by oxidative stress and mediate protective cellular responses such as autophagy. Recent work at the Drosophila neuromuscular junction implicates autophagy as a regulator of synaptic growth via activation of the JNK signaling pathway. We here outline a framework predicating oxidative stress as a major regulator of synaptic function and growth by the activation of JNK/APβ1 and autophagy. Such responses, we suggest, may underpin some forms of synaptic growth responses and synaptic aging. Β© 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 100β110, 2012