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 journalArticle

79 Citations (Scopus)

Abstract

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
Volume1832
Issue number4
Early online date11 Jan 2013
DOIs
Publication statusPublished - Apr 2013

Fingerprint

Glucagon-Like Peptide 1
Type 2 Diabetes Mellitus
Brain
Alzheimer Disease
Neuroprotective Agents
Insulin
Therapeutics
Pathology
Huntington Disease
Parkinson Disease
Dementia
Central Nervous System
Economics
Clinical Trials
Glucose
Pharmaceutical Preparations
Cognitive Dysfunction

Keywords

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

Cite this

Crosstalk between diabetes and brain : glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration. / Duarte, A. I. (Corresponding Author); Candeias, E.; Correia, S. C.; Santos, R. X.; Carvalho, C.; Cardoso, S.; Plácido, A.; Santos, M. S.; Oliveira, C. R.; Moreira, P. I. (Corresponding Author).

In: Biochimica et Biophysica Acta, Vol. 1832, No. 4, 04.2013, p. 527-541.

Research output: Contribution to journalArticle

Duarte, AI, Candeias, E, Correia, SC, Santos, RX, Carvalho, C, Cardoso, S, Plácido, A, Santos, MS, Oliveira, CR & Moreira, PI 2013, 'Crosstalk between diabetes and brain: glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration', Biochimica et Biophysica Acta, vol. 1832, no. 4, pp. 527-541. https://doi.org/10.1016/j.bbadis.2013.01.008
Duarte, A. I. ; Candeias, E. ; Correia, S. C. ; Santos, R. X. ; Carvalho, C. ; Cardoso, S. ; Plácido, A. ; Santos, M. S. ; Oliveira, C. R. ; Moreira, P. I. / Crosstalk between diabetes and brain : glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration. In: Biochimica et Biophysica Acta. 2013 ; Vol. 1832, No. 4. pp. 527-541.
@article{18840ed376a241d3bdc929295568e36a,
title = "Crosstalk between diabetes and brain: glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration",
abstract = "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.",
keywords = "Alzheimer's disease, Brain, Diabetes, Glucagon-like peptide-1 mimetics, Insulin signaling, Neuroprotection",
author = "Duarte, {A. I.} and E. Candeias and Correia, {S. C.} and Santos, {R. X.} and C. Carvalho and S. Cardoso and A. Pl{\'a}cido and Santos, {M. S.} and Oliveira, {C. R.} and Moreira, {P. I.}",
note = "Acknowledgements We are grateful to Funda{\cc}{\~a}o para a Ci{\^e}ncia e a Tecnologia (FCT, projects PTDC/SAU-TOX/117481/2010, PTDC/SAU-NMC/110990/2009, PTDC/SAU-NEU/103325/2008), Portugal, Programa de Est{\'i}mulo {\`a} Investiga{\cc}{\~a}o da Faculdade de Medicina, Universidade de Coimbra, Portugal (PMADSC/2011), Quadro de Refer{\^e}ncia Estrat{\'e}gico Nacional (QREN, project QREN DO-IT) and European Social Fund (fellowship reference SFRH/BPD/26872/2006 to A.I.D.) for financial support.",
year = "2013",
month = "4",
doi = "10.1016/j.bbadis.2013.01.008",
language = "English",
volume = "1832",
pages = "527--541",
journal = "Biochimica et Biophysica Acta",
issn = "0006-3002",
number = "4",

}

TY - JOUR

T1 - Crosstalk between diabetes and brain

T2 - glucagon-like peptide-1 mimetics as a promising therapy against neurodegeneration

AU - Duarte, A. I.

AU - Candeias, E.

AU - Correia, S. C.

AU - Santos, R. X.

AU - Carvalho, C.

AU - Cardoso, S.

AU - Plácido, A.

AU - Santos, M. S.

AU - Oliveira, C. R.

AU - Moreira, P. I.

N1 - Acknowledgements 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.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

KW - Alzheimer's disease

KW - Brain

KW - Diabetes

KW - Glucagon-like peptide-1 mimetics

KW - Insulin signaling

KW - Neuroprotection

UR - http://europepmc.org/abstract/med/23314196

U2 - 10.1016/j.bbadis.2013.01.008

DO - 10.1016/j.bbadis.2013.01.008

M3 - Article

VL - 1832

SP - 527

EP - 541

JO - Biochimica et Biophysica Acta

JF - Biochimica et Biophysica Acta

SN - 0006-3002

IS - 4

ER -