Biochemical pharmacologyOct 10, 2026

A combined GLP-1 and apelin receptor activator may protect brain cells in a mouse model of Parkinson’s disease

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Oct 11, 2026

Abstract

Motor activity improved with the bifunctional peptide ELA and the GLP-1 receptor agonist liraglutide in a mouse model of Parkinson's disease.

Both ELA and liraglutide reduced inflammation responses by decreasing microglial and astrocyte activation and lowering pro-inflammatory cytokine levels.
Synapse numbers in the striatum were increased, along with enhanced expression of synapse-associated proteins.
Gene expression associated with mitochondrial fission was reduced, while mitochondrial fusion gene expressions and morphology were normalized.
ELA showed superior effects compared to liraglutide in some measured parameters, indicating potential benefits of targeting both GLP-1 and APJ pathways.

Simplified

Parkinson's disease (PD) is a chronic disorder with no disease-modifying treatment available. The glucagon-like peptide-1 (GLP-1) class of drugs is on the market to treat diabetes and obesity. GLP-1 drugs have also shown neuroprotective effects in animal models and clinical trials in PD patients. Apelin (APJ) is an adipokine peptide hormone with neuroprotective actions in preclinical studies. Here, we test the effects of a rationally designed bifunctional peptide, namely ELA (exendin-4-linker-apelin), in the MPTP mouse model of PD. The single GLP-1 receptor agonist liraglutide was used as a comparator. Motor activity was improved by both drugs (open field, pole test, Rotarod), and the inflammation response was reduced (activation of microglia and astrocytes, pro-inflammatory cytokine levels). In addition, synapse numbers were improved in the striatum (Golgi strain, TEM), expression of synapse-associated proteins was enhanced, alongside reduced expression of genes that increase mitochondrial fission. Mitochondrial fusion gene expressions (Opa1, Mfn2, Drp1) and mitochondrial morphology were also normalized (TEM). ELA was superior to liraglutide in some, but not all, parameters measured. The results suggest that the rational design of bifunctional peptides targeting both GLP-1 and APJ pathways-with optimized pharmacokinetics and enhanced blood-brain barrier (BBB) permeability-merits further investigation as a strategy for developing more effective treatments for PD.

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A combined GLP-1 and apelin receptor activator may protect brain cells in a mouse model of Parkinson’s disease

Abstract

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