Modulation of GLP-1 signaling as a novel therapeutic approach in the treatment of Alzheimer’s disease pathology

Antonella Tramutola, Andrea Arena, Chiara Cini, D. Allan Butterfield, Eugenio Barone

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations

Abstract

Introduction: Clinical studies suggest a link between peripheral insulin resistance and cognitive dysfunction. Post-mortem analyses of Alzheimer disease (AD) subjects revealed insulin resistance in the brain, suggesting a role of this condition in cognitive deficits observed in AD. In this review, we focus on the glucagon-like peptide-1 (GLP-1) signaling pathway, whose role in the brain is collecting increasing attention because of its association with insulin signaling activation. Areas covered: The role of GLP-1-mediated effects in the brain and how they are affected along the progression of AD pathology is discussed. Furthermore, we provide a comprehensive discussion about the use of GLP-1 mimetics drugs, which have been developed as a treatment for T2DM but seem to possess a number of other physiological properties, including neuroprotective and anti-inflammatory effects, that may be useful to slow AD progression. Expert commentary: The repurposing of antidiabetic drugs for the modulation of brain insulin resistance in AD appears to be of great interest. The beneficial effects on synaptogenesis, neurogenesis, and cell repair as well as the reduction of the chronic inflammatory response, and most importantly the reduction of amyloid plaques in the brain indicate that these drugs have promise as novel treatments for AD.

Original languageEnglish
Pages (from-to)59-75
Number of pages17
JournalExpert Review of Neurotherapeutics
Volume17
Issue number1
DOIs
StatePublished - Jan 2 2017

Bibliographical note

Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.

Keywords

  • Alzheimer disease
  • GLP-1
  • dementia
  • incretins
  • insulin resistance

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Neurology
  • Pharmacology (medical)

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