Galanin Receptors in the Central Nervous System: Exploring Ligand Interactions, Signal Transduction, and Potential Clinical Implications

TL;DR

This paper reviews how galanin receptors in the brain affect signaling pathways and could lead to new treatments for neurological disorders.

Contribution

The paper integrates current knowledge on galanin receptor ligand interactions and signaling to highlight their clinical potential in CNS disorders.

Findings

Galanin receptors (GalR1, GalR2, GalR3) mediate distinct signaling pathways like AC inhibition and calcium signaling.

Targeting galanin receptors shows preclinical promise for treating mood, pain, epilepsy, and neuroprotection.

Endogenous and exogenous ligands help elucidate receptor-specific functions and pharmacological opportunities.

Abstract

Galanin is a highly conserved neuropeptide widely expressed in the central nervous system (CNS), where it regulates neurotransmission, neuroplasticity, and neuroendocrine functions. Its effects are mediated through three G protein-coupled galanin receptor subtypes, GalR1, GalR2, and GalR3, each exhibiting distinct tissue distributions, ligand affinities, and intracellular signaling mechanisms. Endogenous ligands, including galanin, galanin-like peptide (GALP), and spexin, interact with these receptors to trigger receptor-specific pathways, such as adenylyl cyclase (AC) inhibition (GalR1/GalR3) and phospholipase C-mediated calcium signaling (GalR2), enabling modulation of neuronal excitability, neurotransmitter release, and cell survival. Exogenous ligands, including peptide analogs and non-peptide agonists, have further elucidated receptor function and highlighted opportunities for pharmacological intervention. Preclinical evidence demonstrates that targeting galanin receptors (GalRs) can influence mood, cognition, pain perception, epilepsy, metabolic regulation, and neuroprotection, suggesting therapeutic potential across diverse CNS disorders. By integrating knowledge of ligand–receptor interactions and downstream signaling, this review highlights the central role of GalRs in CNS physiology and their emerging relevance as targets for clinical applications.

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