GLP-1-Receptor Agonists in Neurodegeneration: Neurovascular Unit in the Spotlight

Giulia Monti, Diana Gomes Moreira, Mette Richner, Henricus Antonius Maria Mutsaers, Nelson Ferreira, Asad Jan*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperReviewResearchpeer-review

Abstract

Defects in brain energy metabolism and proteopathic stress are implicated in age-related degenerative neuronopathies, exemplified by Alzheimer’s disease (AD) and Parkinson’s disease (PD). As the currently available drug regimens largely aim to mitigate cognitive decline and/or motor symptoms, there is a dire need for mechanism-based therapies that can be used to improve neuronal function and potentially slow down the underlying disease processes. In this context, a new class of pharmacological agents that achieve improved glycaemic control via the glucagon-like peptide 1 (GLP-1) receptor has attracted significant attention as putative neuroprotective agents. The experimental evidence supporting their potential therapeutic value, mainly derived from cellular and animal models of AD and PD, has been discussed in several research reports and review opinions recently. In this review article, we discuss the pathological relevance of derangements in the neurovascular unit and the significance of neuron–glia metabolic coupling in AD and PD. With this context, we also discuss some unresolved questions with regard to the potential benefits of GLP-1 agonists on the neurovascular unit (NVU), and provide examples of novel experimental paradigms that could be useful in improving our understanding regarding the neuroprotective mode of action associated with these agents.

Original languageEnglish
Article number2023
JournalCells
Volume11
Issue13
ISSN2073-4409
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Alzheimer’s disease
  • glucagon-like peptide-1 (GLP-1)
  • neurodegeneration
  • neurovascular unit
  • Parkinson’s disease

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