Crosstalk between diabetes and brain: glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration

A. I. Duarte (Corresponding Author), E. Candeias, S. C. Correia, R. X. Santos, C. Carvalho, S. Cardoso, A. Plácido, M. S. Santos, C. R. Oliveira, P. I. Moreira (Corresponding Author)

Research output: Contribution to journalArticlepeer-review

116 Citations (Scopus)


According to World Health Organization estimates, type 2 diabetes (T2D) is an epidemic (particularly in under development countries) and a socio-economic challenge. This is even more relevant since increasing evidence points T2D as a risk factor for Alzheimer's disease (AD), supporting the hypothesis that AD is a “type 3 diabetes” or “brain insulin resistant state”. Despite the limited knowledge on the molecular mechanisms and the etiological complexity of both pathologies, evidence suggests that neurodegeneration/death underlying cognitive dysfunction (and ultimately dementia) upon long-term T2D may arise from a complex interplay between T2D and brain aging. Additionally, decreased brain insulin levels/signaling and glucose metabolism in both pathologies further suggests that an effective treatment strategy for one disorder may be also beneficial in the other. In this regard, one such promising strategy is a novel successful anti-T2D class of drugs, the glucagon-like peptide-1 (GLP-1) mimetics (e.g. exendin-4 or liraglutide), whose potential neuroprotective effects have been increasingly shown in the last years. In fact, several studies showed that, besides improving peripheral (and probably brain) insulin signaling, GLP-1 analogs minimize cell loss and possibly rescue cognitive decline in models of AD, Parkinson's (PD) or Huntington's disease. Interestingly, exendin-4 is undergoing clinical trials to test its potential as an anti-PD therapy. Herewith, we aim to integrate the available data on the metabolic and neuroprotective effects of GLP-1 mimetics in the central nervous system (CNS) with the complex crosstalk between T2D-AD, as well as their potential therapeutic value against T2D-associated cognitive dysfunction.
Original languageEnglish
Pages (from-to)527-541
Number of pages15
JournalBiochimica et Biophysica Acta
Issue number4
Early online date11 Jan 2013
Publication statusPublished - Apr 2013
Externally publishedYes

Bibliographical note

We are grateful to Fundação para a Ciência e a Tecnologia (FCT, projects PTDC/SAU-TOX/117481/2010, PTDC/SAU-NMC/110990/2009, PTDC/SAU-NEU/103325/2008), Portugal, Programa de Estímulo à Investigação da Faculdade de Medicina, Universidade de Coimbra, Portugal (PMADSC/2011), Quadro de Referência Estratégico Nacional (QREN, project QREN DO-IT) and European Social Fund (fellowship reference SFRH/BPD/26872/2006 to A.I.D.) for financial support.


  • Alzheimer's disease
  • Brain
  • Diabetes
  • Glucagon-like peptide-1 mimetics
  • Insulin signaling
  • Neuroprotection


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