Neuroprotective Potential of Semaglutide in Parkinson’s Disease: Mechanisms, Preclinical Evidence, and Clinical Perspectives
TL;DR
A narrative review evaluates the therapeutic potential of semaglutide in PD, focusing on its molecular mechanisms and preclinical and emerging clinical evidence, and suggests that semaglutide crosses the blood-brain barrier and activates GLP-1 receptors in neuronal and glial cells, reducing microglial activation, neuroinflammation, and oxidative stress while improving mitochondrial function, cellular metabolism, and neuronal survival.
Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, neuroinflammation, oxidative stress, mitochondrial dysfunction, and α-synuclein accumulation. Current treatments mainly provide symptomatic relief and do not substantially alter disease progression, highlighting the need for effective disease-modifying therapies. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has emerged as a potential neuroprotective agent. This narrative review evaluates the therapeutic potential of semaglutide in PD, focusing on its molecular mechanisms and preclinical and emerging clinical evidence. Experimental studies suggest that semaglutide crosses the blood-brain barrier and activates GLP-1 receptors in neuronal and glial cells, reducing microglial activation, neuroinflammation, and oxidative stress while improving mitochondrial function, cellular metabolism, and neuronal survival. It may also reduce α-synuclein aggregation and improve motor and cognitive outcomes in experimental models. Although findings are promising, clinical evidence remains limited. Well-designed randomized trials are needed to establish its efficacy, safety, optimal dosing, and disease-modifying potential in PD.