title: GPE and GPE analogues as promising neuroprotective agents.
abstract: The tripeptide glycine-proline-glutamate (GPE) is the naturally cleaved N-terminal tripeptide of insulin-like growth factor-1 (IGF-1) in brain tissues by an acid protease. Although GPE does not bind to IGF-1 receptors and its mode of action is not clear, in vitro studies have demonstrated its ability to stimulate acetylcholine and dopamine release, as well as to protect neurones from diverse induced brain injures. More importantly, GPE has been shown to have potent neuroprotective effects in numerous animal models of hypoxic-ischemic brain injury and neurodegenerative diseases such as Parkinson's, Alzheimer's and Huntington's diseases. As a consequence, GPE was suggested to be a potential target for the rational design of neuroprotective agents. Unfortunately, the use of GPE as a therapeutic agent is limited because of its unfavorable biochemical and pharmacokinetic properties. This review will focus on structural modifications performed on the GPE molecule in order to obtain bioactive analogues with increased pharmacokinetic profile useful for the treatment of central nervous system (CNS) injures and neurodegenerative disorders.
authors: Dipartimento di Scienze del Farmaco, Universita "G. D'Annunzio", Chieti Scalo (CH), Italy. cacciatore@unich.it
authors: I
authors: I
authors: Cacciatore
authors: C
authors: C
authors: Cornacchia
authors: L
authors: L
authors: Baldassarre
authors: E
authors: E
authors: Fornasari
authors: A
authors: A
authors: Mollica
authors: A
authors: A
authors: Stefanucci
authors: F
authors: F
authors: Pinnen
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000293:injuries; D006801:Humans; D007334:Insulin-Like Growth Factor I; D019636:Neurodegenerative Diseases / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010446:Peptide Fragments
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D007334:Insulin-Like Growth Factor I; C062053:glycyl-prolyl-glutamic acid