Neuroprotective effects of Gly-Pro-Glu, the N-terminal tripeptide of IGF-1, in the hippocampus in vitro.
Insulin-like growth factor 1 (IGF-1) plays a critical role in CNS development. IGF-1 can block neuronal apoptosis in vitro and in vivo. IGF-1 is thought to be cleaved into des-N-(1-3)-IGF-1 and an amino terminal glycine-proline-glutamate (GPE tripeptide). Here we report a neuroprotective role for GPE tripeptide, with enhanced survival of the CA1-2 hippocampal neurons following an excitotoxic insult in vitro. Binding and displacement studies suggest uniquely distributed sites of action within the rat including the hippocampal CA1-2, pyriform cortex, amygdala, choroid plexus, blood vessels and to a lesser extent in the cortical regions. A similar pattern of binding was seen in the human. This finding could lead to new strategies to reduce neuronal death after injury and in disease.
Saura
J
J
Department of Pharmacology, School of Medicine, University of Auckland, New Zealand.
Curatolo
L
L
Williams
C E
CE
Gatti
S
S
Benatti
L
L
Peeters
C
C
Guan
J
J
Dragunow
M
M
Post
C
C
Faull
R L
RL
Gluckman
P D
PD
Skinner
S J
SJ
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000737:chemistry*; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000378:metabolism / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats
D018696:Neuroprotective Agents; D009842:Oligopeptides; D007334:Insulin-Like Growth Factor I; C062053:glycyl-prolyl-glutamic acid