Incretin analogues that have been developed to treat type 2 diabetes hold promise as a novel treatment strategy for Alzheimer's disease

Recent Pat CNS Drug Discov. 2010 Jun;5(2):109-17. doi: 10.2174/157488910791213130.

Abstract

Analogues of the incretins Glucagon-like peptide 1 (GLP-1) and Glucose-dependent insulinotropic peptide (GIP) have been developed to treat type 2 diabetes mellitus. They are protease resistant and have a longer biological half life than the native peptides. Some of these novel analogues can cross the blood-brain barrier, have neuroprotective effects, activate neuronal stem cells in the brain, and can improve cognition. The receptors for GIP and GLP-1 are expressed in neurons, and both GIP and GLP-1 are expressed and released as transmitters by neurons. GIP analogues such as DAla(2)GIP and GLP-1 analogues such as liraglutide enhance synaptic plasticity in the brain and also reverse the betaamyloid induced impairment of synaptic plasticity. In mouse models of Alzheimer's disease, GLP-1 analogues Val(8)GLP-1 and liraglutide prevent memory impairment and the block of synaptic plasticity in the brain. Since two GLP- 1 analogues exendin-4 (Exenatide, Byetta) and liraglutide (Victoza) are already on the market as treatments for Type 2 diabetes, and others are in late stage clinical trials, these drugs show promise as treatments for neurodegenerative diseases such as Alzheimer's disease. Currently, there are three patents covering native GLP-1 and different GLP-1 analogues and one patent for the use of GIP and different GIP analogues for the treatment of neurodegenerative diseases.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Amino Acid Sequence
  • Animals
  • Blood-Brain Barrier / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Gastric Inhibitory Polypeptide / analogs & derivatives
  • Gastric Inhibitory Polypeptide / pharmacology
  • Gastric Inhibitory Polypeptide / therapeutic use*
  • Glucagon-Like Peptide 1 / analogs & derivatives
  • Glucagon-Like Peptide 1 / pharmacology
  • Glucagon-Like Peptide 1 / therapeutic use*
  • Humans
  • Incretins / therapeutic use*
  • Models, Neurological
  • Molecular Sequence Data
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Patents as Topic

Substances

  • Incretins
  • Neuroprotective Agents
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1