Research Progress on Neuroprotective Effects and Mechanisms of Glucagon-like Peptide 1 Analogues in Alzheimer's Disease

Abstract

Glucagon-like peptide 1 (GLP-1) is a kind of incretin produced in the intestinal with multiple pharmacological effects, which can stimulate insulin secretion effectively. Various GLP-1 analogues have been widely used in the treatment of type 2 diabetes mellitus. Alzheimer's disease (AD) is closely related to type 2 diabetes mellitus, with some common pathological features, such as insulin resistance, and epidemiological studies also showed that patients with type 2 diabetes mellitus have an increased risk of developing AD. GLP-1 analogues have shown beneficial effects in both preclinical animal research and clinical trials of AD. Therefore, the authors summarized the main characteristics of GLP-1 and AD, and analyzed the mechanisms of GLP-1 in preclinical AD studies of animal models. GLP-1 readily crosses the blood-brain barrier and exerts its neuroprotective effects by binding to and activating the widely distributed GLP-1 receptors (GLP-1Rs) in the brain, affecting multiple physiological and pathological processes including glucose metabolism, neuroinflammation, mitochondrial function, and cell proliferation. Insulin resistance and inflammation are key common pathways in AD and type 2 diabetes. GLP-1 may exert its neuroprotective effects by improving mitochondrial function and glycolysis, reducing oxidative stress levels, exerting anti-inflammatory and anti-apoptotic effects, inducing neurogenesis, and inhibiting glial cell proliferation. This paper maybe provide the reference for further study of GLP-1 analogues in AD, hoping to open new therapy venues for AD patients.

Keywords

• glucagon-like peptide 1
• alzheimer's disease
• amyloid β-protein
• neuroprotective effect