BACKGROUND: Cellular mechanisms aimed at repairing protein damage and maintaining homeostasis, widely understood to be triggered by the damage itself, have recently been shown to be under cell nonautonomous control in the metazoan @entity2199 . The @entity1457 response (HSR) is one such conserved mechanism, activated by cells upon exposure to proteotoxic conditions such as heat. Previously, we had shown that this conserved cytoprotective response is regulated by the thermosensory neuronal circuitry of @entity2199 . Here, we investigate the mechanisms and physiological relevance of neuronal control. RESULTS: By combining optogenetic methods with live visualization of the dynamics of the @entity1457 transcription factor ( @entity27478 ), we show that excitation of the AFD thermosensory neurons is sufficient to activate @entity27478 in another cell, even in the absence of temperature increase. Excitation of the AFD thermosensory neurons enhances @entity750 release. @entity750 release elicited by direct optogenetic stimulation of serotonergic neurons activates @entity27478 and upregulates molecular chaperones through the metabotropic @entity750 receptor @entity50040 . Consequently, excitation of serotonergic neurons alone can suppress protein misfolding in @entity2199 peripheral tissue. CONCLUSIONS: These studies imply that thermosensory activity coupled to serotonergic signaling is sufficient to activate the protective HSR prior to @entity16 . The ability of neurosensory release of @entity750 to control cellular stress responses and activate @entity27478 has powerful implications for the treatment of protein conformation diseases.

Neuronal XXXX release triggers the @entity1457 response in @entity2199 in the absence of temperature increase.

@entity2199 :: ('6239', 'Species') :: ['C. elegans'] @entity1457 :: ('MESH:D012769', 'Disease') :: ['heat shock'] @entity16 :: ('MESH:D009422', 'Disease') :: ['frank proteotoxic damage'] @entity50040 :: ('181716(Tax:6239)', 'Gene') :: ['SER-1'] @entity750 :: ('MESH:D012701', 'Chemical') :: ['serotonin', 'Serotonin'] @entity27478 :: ('173078(Tax:6239)', 'Gene') :: ['HSF1']
@entity750 :: (MESH:D012701,Chemical) :: ['serotonin']
