GLP-1 Receptor Agonists show broad neuroprotective potential in neuropathic pain and neurodegenerative diseases

Current treatments for neuropathic pain often provide incomplete relief, while neurodegenerative diseases like Alzheimer's and Parkinson's lack disease-modifying therapies. Both conditions share underlying pathophysiological mechanisms, including chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired insulin signaling. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs), initially developed for type 2 diabetes mellitus, have shown promising neuroprotective and anti-inflammatory effects, suggesting a potential to address these shared neurological challenges beyond their metabolic indications.

This comprehensive review synthesized findings from preclinical and early clinical studies investigating the therapeutic potential of GLP-1RAs. The authors systematically examined their mechanisms of action and observed effects across neuropathic pain and major neurodegenerative diseases, specifically Alzheimer's and Parkinson's disease. The review focused on how GLP-1RAs modulate shared pathophysiological pathways, including chronic neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired insulin signaling, to identify convergent therapeutic strategies and future research directions.

The review highlights that GLP-1RAs exert multifaceted neuroprotective, anti-inflammatory, and autophagy-enhancing effects. In models of neuropathic pain, GLP-1RAs consistently attenuate neuroinflammation and reduce central sensitization, contributing to their analgesic properties. For neurodegenerative diseases, including Alzheimer's and Parkinson's, GLP-1RAs promote neuronal survival, restore metabolic homeostasis, and actively counteract protein aggregation and autophagic dysfunction. These beneficial actions are mediated through the modulation of critical cellular processes such as oxidative stress, mitochondrial function, and insulin signaling pathways.

The convergence of these neuroprotective, anti-inflammatory, and autophagy-enhancing effects positions GLP-1RAs as potential disease-modifying agents across both neuropathic pain and neurodegenerative disorders, offering a unified therapeutic approach.