Poupon-Bejuit, L;
Hughes, MP;
Liu, W;
Geard, A;
Faour-Slika, N;
Whaler, S;
Massaro, G;
(2022)
A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease.
Scientific Reports
, 12
(1)
, Article 13825. 10.1038/s41598-022-17338-1.
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Massaro_A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease_VoR.pdf - Published Version Download (2MB) | Preview |
Abstract
Infantile neuroaxonal dystrophy (INAD) is a rare paediatric neurodegenerative condition caused by mutations in the PLA2G6 gene, which is also the causative gene for PARK14-linked young adult-onset dystonia parkinsonism. INAD patients usually die within their first decade of life, and there are currently no effective treatments available. GLP1 receptor (GLP-1R) agonists are licensed for treating type 2 diabetes mellitus but have also demonstrated neuroprotective properties in a clinical trial for Parkinson's disease. Therefore, we evaluated the therapeutic efficacy of a new recently licensed GLP-1R agonist diabetes drug in a mouse model of INAD. Systemically administered high-dose semaglutide delivered weekly to juvenile INAD mice improved locomotor function and extended the lifespan. An investigation into the mechanisms underlying these therapeutic effects revealed that semaglutide significantly increased levels of key neuroprotective molecules while decreasing those involved in pro-neurodegenerative pathways. The expression of mediators in both the apoptotic and necroptotic pathways were also significantly reduced in semaglutide treated mice. A reduction of neuronal loss and neuroinflammation was observed. Finally, there was no obvious inflammatory response in wild-type mice associated with the repeated high doses of semaglutide used in this study.
| Type: | Article |
|---|---|
| Title: | A GLP1 receptor agonist diabetes drug ameliorates neurodegeneration in a mouse model of infantile neurometabolic disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-022-17338-1 |
| Publisher version: | https://doi.org/10.1038/s41598-022-17338-1 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Animals, Diabetes Mellitus, Type 2, Disease Models, Animal, Dystonic Disorders, Group VI Phospholipases A2, Mice, Neuroaxonal Dystrophies, Parkinsonian Disorders |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10154191 |
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