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- Title
The Dual GLP-1/GIP Receptor Agonist DA4-JC Shows Superior Protective Properties Compared to the GLP-1 Analogue Liraglutide in the APP/PS1 Mouse Model of Alzheimer's Disease.
- Authors
Maskery, Mark; Goulding, Elizabeth Mary; Gengler, Simon; Melchiorsen, Josefine Ulrikke; Rosenkilde, Mette Marie; Hölscher, Christian
- Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder for which there is no cure. Here, we test a dual GLP-1/GIP receptor agonist (DA4-JC) that has a cell penetrating sequence added to enhance blood-brain barrier penetration. We show in a receptor activity study that DA4-JC has balanced activity on both GLP-1 and GIP receptors but not on GLP-2 or Glucagon receptors. A dose-response study in the APP/PS1 mouse model of AD showed both a dose-dependent drug effect on the inflammation response and the reduction of amyloid plaques in the brain. When comparing DA4-JC with the GLP-1 analogue liraglutide at equal doses of 10nmol/kg bw ip. once-daily for 8 weeks, DA4-JC was more effective in reversing memory loss, enhancing synaptic plasticity (LTP) in the hippocampus, reducing amyloid plaques and lowering pro-inflammatory cytokine levels in the brain. The results suggest that DA4-JC may be a novel treatment for AD.
- Subjects
ALZHEIMER'S disease; ANIMAL experimentation; BIOLOGICAL models; BLOOD-brain barrier; CELL receptors; CYTOKINES; DOSE-effect relationship in pharmacology; INFLAMMATION; MEMORY disorders; MICE; NEUROPLASTICITY; TREATMENT effectiveness; GLUCAGON-like peptides; GLUCAGON-like peptide-1 agonists; AMYLOID plaque
- Publication
American Journal of Alzheimer's Disease & Other Dementias, 2020, Vol 35, p1
- ISSN
1533-3175
- Publication type
Article
- DOI
10.1177/1533317520953041