title: Oxidative stress and autophagy: mediators of synapse growth?
abstract: Many neurodegenerative conditions have oxidative stress burdens where levels of reactive oxygen species (ROS) exceed the antioxidant capacity of the neuron. ROS can induce wide-ranging damage in a cell and this is prevented by the activation of antioxidant responses including autophagy. Jun-kinase (JNK) is stimulated by ROS and mediates antioxidant responses via the activation of the transcriptional activators Fos and Jun (AP-1). In recently published work we examined Drosophila mutants with overgrown larval neuromuscular synapses, mutants that also show all the hallmarks of lysosomal storage disease (LSD). We find that we can reverse this synaptic overgrowth by reducing the oxidative stress burden, and that synaptic overgrowth is mediated by autophagy and JNK-AP-1 activity. We also examined animals defective for protection from oxidative stress and found that they too have synapse overgrowth generated by JNK-AP-1 activity. Treatment of larvae with a known ROS-generating toxin, paraquat, yielded similar synaptic responses. The observations that oxidative stress responses, potentially acting through autophagy, can generate synaptic growth suggest that ROS may be a potent regulator of synapse size and function. These findings have intriguing implications for aging neurons, neurodegenerative conditions and the interpretation of metabolic demand during learning and memory.
authors.affiliation: Department of Biology and Hull-York Medical School, University of York, York, UK.
authors.forename: Ryan J H
authors.initials: RJ
authors.lastname: West
authors.forename: Sean T
authors.initials: ST
authors.lastname: Sweeney
mesh_terms: D000818:Animals; D001343:Autophagy; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000201:enzymology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000378:metabolism; D018384:Oxidative Stress; D013569:Synapses / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; D018808:Transcription Factor AP-1; C429164:spin protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases