# Liraglutide attenuates aluminum chloride-induced Alzheimer’s disease in rats by modulating the oxLDL/LPA/LPAR1 pathway

## TL;DR

Liraglutide helps reduce Alzheimer's symptoms in rats by targeting a specific pathway involving oxidized LDL and lysophosphatidic acid.

## Contribution

This study is the first to show liraglutide's neuroprotective effects via the oxLDL/LPA/LPAR1/BACE1 pathway in an Alzheimer's rat model.

## Key findings

- Liraglutide reduces anxiety, depression, and memory deficits in rats with Alzheimer's.
- Liraglutide lowers levels of oxLDL, LPA, LPAR1, and BACE1 in the hippocampus.
- Liraglutide preserves brain structure and shows antioxidant and anti-apoptotic effects.

## Abstract

Aluminum toxicity in rodents is well documented to be used for inducing experimental models that mimic the clinical phenotypes of Alzheimer’s disease (AD). Liraglutide is a well-known antidiabetic drug promising for modulating neurodegenerative conditions. Thus, investigating the ameliorative effects of Liraglutide on AD induced by aluminum chloride (AlCl3), highlighting the role of lysophosphatidic acid (LPA)/ β-secretase 1 (BACE1), is promising. Male rats are subdivided into four groups. Except for the normal group, animals are subjected to daily administration of AlCl3 (70 mg/kg, i.p.) for 45 days. Along with AlCl3, Liraglutide (0.3 mg/kg twice daily, s.c.) and Donepezil (1 mg/kg daily, i.p.) therapy are administered in AlCl3 + Lira and AlCl3 + Done groups, respectively. Liraglutide significantly ameliorates AlCl3-induced anxiety, depression-like behaviors, and deficits in memory functions. Liraglutide therapy retains the histopathological structure of the brain, with antioxidant and anti-apoptotic abilities. Moreover, Liraglutide successfully decreases hippocampal levels of oxidized low-density lipoprotein (oxLDL), LPA, lysophosphatidic acid receptor 1 (LPAR1), and β-secretase 1 (BACE1) compared with the AlCl3 group. Thus, liraglutide shows neuroprotective effects mediated by downregulation of the oxLDL/LPA/LPAR1/BACE1 pathway, which is studied for the first time to our knowledge.

Mechanistic insights into liraglutide-mediated neuroprotection reveal modulation of oxidized LDL and lysophosphatidic acid signalling in an experimental rat model of Alzheimer’s disease.