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Neuroprotective Actions of Glucagon-Like Peptide-1 (GLP-1) Analogues in Alzheimer’s and Parkinson’s Diseases

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Abstract

The current absence of effective treatments for Alzheimer’s disease (AD) and Parkinson’s disease (PD) reflects an incomplete knowledge of the underlying disease processes. Considerable efforts have been made to investigate the central pathological features of these diseases, giving rise to numerous attempts to develop compounds that interfere with such features. However, further characterization of the molecular targets within the interconnected AD and PD pathways is still required. Impaired brain insulin signaling has emerged as a feature that contributes to neuronal dysfunction in both AD and PD, leading to strategies aiming at restoring this pathway in the brain. Long-acting glucagon-like peptide-1 (GLP-1) analogues marketed for treatment of type 2 diabetes mellitus have been tested and have shown encouraging protective actions in experimental models of AD and PD as well as in initial clinical trials. We review studies revealing the neuroprotective actions of GLP-1 analogues in pre-clinical models of AD and PD and promising results from recent clinical trials.

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Acknowledgements

The authors acknowledge the use of Mind the Graph (http://www.mindthegraph.com) for the design of the figure in this work.

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  1. Andre F. Batista and Victor Bodart-Santos contributed equally to this work.

Authors and Affiliations

  1. Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21944-590, Brazil

    Andre F. Batista, Victor Bodart-Santos, Fernanda G. De Felice & Sergio T. Ferreira

  2. Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21941-902, Brazil

    Victor Bodart-Santos

  3. Department of Psychiatry, Centre for Neuroscience Studies, Queen’s University, Kingston, Ontario, K7L 3N6, Canada

    Fernanda G. De Felice

  4. Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, RJ, 21944-590, Brazil

    Sergio T. Ferreira

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AFB, VBS, FGDF and STF have no conflicts of interest that are directly relevant to the content of this article.

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Work in the authors’ groups has been supported by the National Institute for Translational Neuroscience (Brazil), the Brazilian agencies Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) (to STF and FDF), and Alzheimer Society Canada and Weston Brain Institute (to FDF). AFB and VBS are supported by post-doctoral and pre-doctoral fellowships, respectively, from CNPq.

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Batista, A.F., Bodart-Santos, V., De Felice, F.G. et al. Neuroprotective Actions of Glucagon-Like Peptide-1 (GLP-1) Analogues in Alzheimer’s and Parkinson’s Diseases. CNS Drugs 33, 209–223 (2019). https://doi.org/10.1007/s40263-018-0593-6

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