The Role for IGF-1-derived Small Neuropeptides as a Therapeutic Target for Neurological Disorders

Expert Opin Ther Targets. 2015 Jun;19(6):785-93. doi: 10.1517/14728222.2015.1010514. Epub 2015 Feb 5.

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords: IGF-1; Parkinson’s disease; cyclic glycine-proline; glycine-proline-glutamate; ischemic brain injury; rat.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Design
  • Humans
  • Insulin-Like Growth Factor I / administration & dosage
  • Insulin-Like Growth Factor I / chemistry
  • Insulin-Like Growth Factor I / pharmacology*
  • Molecular Targeted Therapy
  • Nervous System Diseases / drug therapy*
  • Nervous System Diseases / physiopathology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / physiopathology
  • Neuropeptides / administration & dosage
  • Neuropeptides / pharmacokinetics
  • Neuropeptides / pharmacology
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacokinetics
  • Neuroprotective Agents / pharmacology*

Substances

  • Neuropeptides
  • Neuroprotective Agents
  • Insulin-Like Growth Factor I