Abstract: Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), originally developed for type 2 diabetes mellitus, have demonstrated significant neuroprotective and analgesic properties in preclinical and early clinical studies. This review examines the role of GLP-1RAs and their therapeutic potential in neuropathic pain and neurodegenerative diseases, which share several overlapping pathophysiological mechanisms. These include chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired insulin signaling, and altered synaptic plasticity. In neuropathic pain, GLP-1RAs attenuate neuroinflammation and reduce central sensitization. In neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease, they promote neuronal survival, restore metabolic homeostasis, and counteract protein aggregation and autophagic dysfunction. The convergence of these mechanisms supports the exploration of GLP-1RAs as a unified therapeutic approach across neuroinflammatory and neurodegenerative fields. GLP-1RAs exert multifaceted neuroprotective, anti-inflammatory, and autophagy-enhancing effects, highlighting their potential as disease-modifying agents in neuropathic pain and neurodegenerative disorders. Further studies are needed to optimize CNS delivery, refine patient selection, and evaluate long-term safety.
Grasso et al. (Wed,) studied this question.