Propionyl-IIGL tetrapeptide antagonizes beta-amyloid excitotoxicity in rat nucleus basalis

Neuroreport. 1999 Jun 3;10(8):1693-8. doi: 10.1097/00001756-199906030-00013.


A putative tetrapeptide beta-amyloid (Abeta) antagonist (propionyl-Ile-Ile-Gly-Leu [Pr-IIGL]) based on the [31-34] sequence of Abeta was previously shown to rescue astrocytes from Abeta-induced membrane depolarization and subsequent long-term elevations of the intracellular Ca2+ concentration in vitro. Here we provide in vivo evidence that the Pr-IIGL tetrapeptide effectively attenuates the excitotoxic action of Abeta(1-42) on cholinergic neurons of the rat magnocellular nucleus basalis (MBN). We also demonstrate by means of microdialysis that administration of Pr-IIGL abolished Abeta(1-42)-induced increases in extracellular aspartate and glutamate concentrations in the MBN, which coincide with a significant preservation of cholinergic MBN neurons and their cortical projections. This neuroprotective effect was associated with preserved exploratory behavior in an open-field paradigm, and improved memory retention in a step-through passive avoidance task. Our data presented here indicate for the first time the efficacy of short, modified functional Abeta antagonists in ameliorating Abeta excitotoxicity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Amyloid beta-Peptides / antagonists & inhibitors
  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Aspartic Acid / metabolism
  • Avoidance Learning / drug effects
  • Basal Nucleus of Meynert / anatomy & histology
  • Basal Nucleus of Meynert / drug effects*
  • Basal Nucleus of Meynert / metabolism
  • Behavior, Animal / drug effects
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Glutamic Acid / metabolism
  • Histocytochemistry
  • Male
  • Microdialysis
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Oligopeptides / pharmacology*
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / toxicity*
  • Rats
  • Rats, Wistar
  • Taurine / metabolism


  • Amyloid beta-Peptides
  • Neuroprotective Agents
  • Oligopeptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • propionyl-isoleucyl-isoleucyl-glycyl-leucinamide
  • Taurine
  • Aspartic Acid
  • Glutamic Acid
  • Acetylcholinesterase