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Galanin (GAL) and GAL receptors (GALR) are overexpressed in degenerating brain regions associated with cognitive decline in Alzheimer's disease (AD). The functional consequences of GAL plasticity in AD are unclear. GAL inhibits cholinergic transmission in the hippocampus and impairs spatial memory in rodent models, suggesting that GAL overexpression exacerbates cognitive impairment in AD. By contrast, gene expression profiling of individual cholinergic basal forebrain (CBF) neurons aspirated from AD tissue revealed that GAL hyperinnervation positively regulates mRNAs that promote CBF neuronal function and survival. GAL also exerts neuroprotective effects in rodent models of neurotoxicity. These data support the growing concept that GAL overexpression preserves CBF neuron function, which may in turn delay the onset of symptoms of AD. Further elucidation of GAL activity in selectively vulnerable brain regions will help gauge the therapeutic potential of GALR ligands in the treatment of AD.

Since the discovery of galanin in 1983, one of the most frequently suggested physiological function for this peptide is pain modulation at the level of the spinal cord. This notion, initially based on the preferential distribution of galanin in dorsal spinal cord, has been supported by results from a large number of morphological, molecular, and functional studies. It is generally agreed that spinally applied galanin produces a biphasic, dose-dependent effect on spinal nociception through activation of GalR1 (inhibitory) or GalR2 (excitatory) receptors. Galanin also appears to have an endogenous inhibitory role, particularly after peripheral nerve injury when the synthesis of galanin is increased in sensory neurons. In recent years, small molecule ligands of galanin receptors have been developed, which may lead to the development of analgesic drugs, which affects the galanin system at the spinal cord level.