Glucagon-Like Peptide-1 Receptor Agonists in Neurodegenerative Diseases: A Comprehensive Review

Abstract

There is a steadily increasing global burden of neurodegenerative diseases (NDs) such as dementia, including Alzheimer's disease (AD), and movement disorders like Parkinson's disease (PD), which emphasizes the importance of disease-modifying therapy (as opposed to symptomatic therapy). This review considers a new disease-modifying strategy through the so-called glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in these NDs, and the mechanistic rationale and evidence base. The review considers a multi-targeting strategy, translational issues, and a future research agenda. Translational challenges for these agents are also discussed, particularly the need to understand how the timing of treatment may influence outcomes. The review also considers unwanted side effects like unintended weight loss, which may compromise "at-risk" patient groups. In conclusion, GLP-1 RAs are an intriguing multitarget treatment option for people with NDs, and future research should focus on optimizing treatment for clinical trials, evolved agonists that can penetrate the central nervous system (CNS), and combination therapies.