CEP-1347 promotes survival of NGF responsive neurones in primary DRG explants.
CEP-1347 inhibits the signalling pathway of c-jun-N-terminal kinase, and is neuroprotective in vivo and in vitro. Embryonic chick dorsal root ganglion neurones are dependent on NGF for survival and neurite outgrowth; NGF withdrawal results in apoptotic cell death. We examined the neuroprotective and neurite outgrowth promoting activity of CEP-1347 in dissociated DRG neurones and in primary DRG explants. CEP-1347 was as effective as NGF in promoting survival of dissociated DRG neurones, but caused only limited neurite outgrowth from DRG explants. When NGF was subsequently added to CEP-1347 treated explants, the outgrowth increased to a similar level to explants which had received NGF throughout. CEP-1347 may be a useful tool to maintain viable DRG explants to allow evaluation of neurite outgrowth promoting compounds and dissection of survival and neurite outgrowth signalling pathways.
Bilsland
James G
JG
Department of Biochemistry and Molecular Biology, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Harper
Sarah J
SJ
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology
D002227:Carbazoles; D007211:Indoles; C106592:3,9-bis((ethylthio)methyl)-K-252a; D020932:Nerve Growth Factor