Neuroprotective effects of glucose-dependent insulinotropic polypeptide in Alzheimer's disease

Rev Neurosci. 2016 Jan;27(1):61-70. doi: 10.1515/revneuro-2015-0021.

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a member of the incretin hormones and growth factors. Neurons express the GIP receptor, and GIP and its agonists can pass through the blood brain barrier and show remarkable neuroprotective effects by protecting synapse function and numbers, promoting neuronal proliferation, reducing amyloid plaques in the cortex and reducing the chronic inflammation response of the nervous system. Long-acting analogues of GIP that are protease resistant had been developed as a treatment for type 2 diabetes. It has been found that such GIP analogues show good protective effects in animal models of Alzheimer's disease. Novel dual agonist peptides that activate the GIP receptor and another incretin receptor, glucagon-like peptide -1 (GLP-1), are under development that show superior effects in diabetic patients compared to single GLP-1 agonists. The dual agonists also show great promise in treating neurodegenerative disorders, and there are currently several clinical trials ongoing, testing GLP-1 mimetics in people with Alzheimer's or Parkinson's disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / prevention & control
  • Animals
  • Gastric Inhibitory Polypeptide / analogs & derivatives*
  • Gastric Inhibitory Polypeptide / pharmacology
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Receptors, Gastrointestinal Hormone / agonists
  • Signal Transduction
  • Synapses / drug effects

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Neuroprotective Agents
  • Receptors, Gastrointestinal Hormone
  • Gastric Inhibitory Polypeptide
  • gastric inhibitory polypeptide receptor