A new Alzheimer's disease interventive strategy: GLP-1

Curr Drug Targets. 2004 Aug;5(6):565-71. doi: 10.2174/1389450043345245.


Glucagon-like peptide-1 (7-36)-amide (GLP-1) is an endogenous 30-amino acid gut peptide, which binds at the GLP-1 receptor coupled to the cyclic AMP second messenger pathway. GLP-1 receptor stimulation enhances pancreatic islet beta-cell proliferation, glucose-dependent insulin secretion and lowers blood glucose and food intake in patients with type 2 diabetes mellitus. Not limited to the pancreas, the chemoarchitecture of GLP-1 receptor distribution in the brain of rodents and humans correlates with a central role for GLP-1 in the regulation of food intake. However emerging evidence suggests that stimulation of neuronal GLP-1 receptors plays an important role in regulating neuronal plasticity and cell survival. GLP-1 has been documented to induce neurite outgrowth and to protect against excitotoxic cell death and oxidative injury in cultured neuronal cells. Moreover, GLP-1 and exendin-4, a naturally occurring more stable analogue of GLP-1 that likewise binds at the GLP-1 receptor, were shown to reduce endogenous levels of amyloid-beta peptide (Abeta) in mouse brain and to reduce levels of beta-amyloid precursor protein (betaAPP) in neurons. Collectively these data suggest that treatment with GLP-1 or a related peptide beneficially affects a number of the therapeutic targets associated with Alzheimer's disease (AD). Although much remains to be elucidated with regards to the downstream signaling pathways involved in the pro-survival properties of GLP-1, modulation of calcium homeostasis may be critical. This review will consider the potential therapeutic relevance of GLP-1 to CNS disorders, such as AD.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / prevention & control*
  • Animals
  • Calcium / metabolism
  • Cell Death / drug effects
  • Cell Death / physiology
  • Glucagon / chemistry
  • Glucagon / pharmacology*
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Homeostasis / drug effects
  • Homeostasis / physiology
  • Humans
  • Models, Biological
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacology*
  • Peptide Fragments / physiology*
  • Protein Precursors / chemistry
  • Protein Precursors / pharmacology*
  • Protein Precursors / physiology*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology


  • Peptide Fragments
  • Protein Precursors
  • Glucagon-Like Peptide 1
  • Glucagon
  • Calcium