title: The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders.
abstract: BACKGROUND
  Exogenous IGF-1 protects the brain from ischemic injury and improves function. However, its clinical application to neurological disorders is limited by its large molecular size, poor central uptake and mitogenic potential.
  
  
  METHODS
  In this review, the authors have discussed the efficacy, pharmacokinetics and mechanisms of IGF-1 derivatives on protecting acute brain injury, preventing memory impairment and improving recovery from neurological degenerative conditions evaluated in various animal models. We have included natural metabolites of IGF-1, glycine-proline-glutamate (GPE), cleaved from N-terminal IGF-1 and cyclic glycine-proline (cGP) as well as the structural analogues of GPE and cGP, glycine-2-methyl-proline-glutamate and cyclo-l-glycyl-l-2-allylproline, respectively. In addition, the regulatory role for cGP in bioavailability of IGF-1 has also been discussed.
  
  
  CONCLUSIONS
  These small neuropeptides provide effective neuroprotection by offering an improved pharmacokinetic profile and more practical route of administration compared with IGF-1 administration. Developing modified neuropeptides to overcome the limitations of their endogenous counterparts represents a novel strategy of pharmaceutical discovery for neurological disorders. The mechanism of action may involve a regulation of IGF-1 bioavailability.
authors: University of Auckland, Liggins Institute , Private Bag 92019, Auckland , New Zealand +64 93 737 599 ext. 86134 ; +64 93 082 385 ; j.guan@auckland.ac.nz.
authors: Jian
authors: J
authors: Guan
authors: Paul
authors: P
authors: Harris
authors: Margaret
authors: M
authors: Brimble
authors: Yang
authors: Y
authors: Lei
authors: Jun
authors: J
authors: Lu
authors: Yang
authors: Y
authors: Yang
authors: Alistair J
authors: AJ
authors: Gunn
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000503:physiopathology; D009479:Neuropeptides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D009479:Neuropeptides; D018696:Neuroprotective Agents; D007334:Insulin-Like Growth Factor I
keywords: IGF-1; Parkinson’s disease; cyclic glycine-proline; glycine-proline-glutamate; ischemic brain injury; rat