title: MAP kinase pathways in neuronal cell death.
abstract: The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogen-activated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen-activated protein kinases activated by extracellular stimuli including stress, are a major focus. Knock-out mouse studies have demonstrated that removing particular JNK genes can reduce the severity in various disease scenarios, including those which are used to model Parkinson's disease and cerebral ischemia. In addition, activation of JNKs can be seen in human disease tissue. In this review we bring together the evidence for JNK being an important regulator of neuronal loss and outline the advancement of small molecule inhibitors for future therapeutic intervention.
authors.affiliation: Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline Research & Development Limited, New Frontiers Science Park, Third Avenue, CM19 5AW, Harlow, Essex, UK. Karen.L.philpott@gsk.com
authors.forename: Karen L
authors.initials: KL
authors.lastname: Philpott
authors.forename: Laura
authors.initials: L
authors.lastname: Facci
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002493:Central Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases