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
Research output: Contribution to journal › Journal article › Research › peer-review
Documents
- Open Access version
Final published version, 933 KB, PDF document
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.
Original language | English |
---|---|
Article number | 1533317520953041 |
Journal | American Journal of Alzheimer's Disease and Other Dementias |
Volume | 35 |
Number of pages | 11 |
ISSN | 1533-3175 |
DOIs | |
Publication status | Published - 2020 |
- insulin, growth factor, brain, inflammation, TNF-alpha, synaptic plasticity
Research areas
Number of downloads are based on statistics from Google Scholar and www.ku.dk
ID: 257084133