Glucagon-like peptide-1 decreases endogenous amyloid-β peptide (Aβ) levels and protects hippocampal neurons from death induced by Aβ and iron

Tracy Ann Perry, Debomoy K. Lahiri, Kumar Sambamurti, Demao Chen, Mark P. Mattson, Josephine M. Egan, Nigel H. Greig

Research output: Contribution to journalArticle

265 Scopus citations

Abstract

Glucagon-like peptide-1(7-36)-amide (GLP-1) is an endogenous insulinotropic peptide that is secreted from the gastrointestinal tract in response to food. It enhances pancreatic islet β-cell proliferation and glucose-dependent insulin secretion and lowers blood glucose and food intake in patients with type 2 diabetes mellitus. GLP-1 receptors, which are coupled to the cyclic AMP second messenger pathway, are expressed throughout the brains of rodents and humans. It was recently reported that GLP-1 and exendin-4, a naturally occurring, more stable analogue of GLP-1 that binds at the GLP-1 receptor, possess neurotrophic properties and can protect neurons against glutamate-induced apoptosis. We report here that GLP-1 can reduce the levels of amyloid-β peptide (Aβ) in the brain in vivo and can reduce levels of amyloid precursor protein (APP) in cultured neuronal cells. Moreover, GLP-1 and exendin-4 protect cultured hippocampal neurons against death induced by Aβ and iron, an oxidative insult. Collectively, these data suggest that GLP-1 can modify APP processing and protect against oxidative injury, two actions that suggest a novel therapeutic target for intervention in Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)603-612
Number of pages10
JournalJournal of Neuroscience Research
Volume72
Issue number5
DOIs
StatePublished - Jun 1 2003

Keywords

  • Alzheimer's disease
  • Apoptosis
  • NGF
  • Oxidative stress
  • PC12 cell

ASJC Scopus subject areas

  • Neuroscience(all)

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