**GALR1 Quick Facts**
Property
Value
Gene Symbol GALR1
Full Name Galanin Receptor 1
Chromosome 18q23
NCBI Gene ID 25826
Ensembl ID ENSG00000134390
UniProt ID P47211
OMIM 600041
Protein Length 349 amino acids
Primary Function G protein-coupled receptor for galanin
Expression CNS (hippocampus , cortex , hypothalamus), peripheral nervous system
Associated Diseases AD, PD, epilepsy, depression, anxiety
GALR1 (Galanin Receptor 1 ) is a G protein-coupled receptor (GPCR) that binds the neuropeptide galanin. Located on chromosome 18q23, this gene encodes a 349-amino acid protein that is expressed primarily in the central nervous system, including the hippocampus, cortex, hypothalamus, and limbic system.
Galanin and its receptors, particularly GALR1, play important roles in modulating neurotransmitter systems, neuronal survival, neuroprotection, and various behavioral functions. Dysregulation of the galanin system has been implicated in Alzheimer's disease, Parkinson's disease, epilepsy, depression, and anxiety disorders, making GALR1 an attractive therapeutic target.
¶ Gene Structure and Protein ArchitectureThe GALR1 gene spans approximately 35 kb and consists of 4 exons encoding a 349-amino acid GPCR protein with seven transmembrane domains. The gene is evolutionarily conserved across mammals.
flowchart TD
A["N-terminus\n(Extracellular)"] --> B["TM1"]
B --> C["TM2"]
C --> D["TM3"]
D --> E["TM4"]
E --> F["TM5"]
F --> G["TM6"]
G --> H["TM7"]
H --> I["C-terminus\n(Intracellular)"]
J["Galanin Binding"] <- A
K["G Protein\nCoupling"] <- I
L["Beta-arrestin\nRecruitment"] <- I
N-terminal Extracellular Domain : Galanin binding siteSeven Transmembrane Domains (TM1-7) : Classic GPCR structureIntracellular C-terminal : G protein coupling and phosphorylation sites
GALR1 couples to multiple G protein subtypes:
Gi/o Coupling : Inhibits adenylate cyclase, reduces cAMPGq Coupling : Activates phospholipase C pathwayBeta-arrestin Pathways : Arrestin-dependent signalingMAPK Activation : Triggers downstream signaling cascades
Agonists : Galanin, galnon, galamide derivativesAntagonists : M35, C7, SNAP 37889, SNAP 398299Allosteric Modulators : Potential for subtype-selective compounds
GALR1 activation modulates:
cAMP/PKA Pathway : Gi-mediated inhibitionMAPK/ERK Pathway : Via Gi and beta-arrestinPI3K/Akt Pathway : Neuroprotective signalingCalcium Signaling : Modulation of intracellular calcium
GALR1 is highly expressed in:
Hippocampus : CA1-CA3 regions, dentate gyrusCortex : Layers II-IV, pyramidal neurons Hypothalamus : Preoptic area, arcuate nucleusAmygdala : Central nucleus, basolateral complexLocus Coeruleus : Noradrenergic neuronsDorsal Raphe : Serotonergic neurons
Neuronal Cell Bodies : Perikaryal localizationDendrites : Synaptic and extrasynaptic receptorsAxon Terminals : Presynaptic modulation
GALR1 dysfunction contributes to AD pathogenesis:
Cholinergic Dysfunction : Galanin co-localizes with cholinergic neurons; increased galanin in AD brain may represent compensatory responseAmyloid Effects : Galanin modulates amyloid precursor protein processingMemory Function : GALR1 signaling affects hippocampal-dependent learningNeuroprotection : GALR1 activation protects against excitotoxicity
In PD, GALR1:
Dopaminergic Protection : Galanin protects dopaminergic neuronsMotor Function : Modulates basal ganglia circuitryNon-Motor Symptoms : Affects mood and autonomic function
GALR1 plays important roles in seizure modulation:
Seizure Suppression : Galanin is anticonvulsantHippocampal Protection : Prevents seizure-induced neuronal damageStatus Epilepticus : Altered expression in chronic epilepsy
¶ Mood and Behavioral Disorders¶ Depression and AnxietyGALR1 is implicated in mood disorders:
Depressive-like Behavior : GALR1 knockout mice show antidepressant-like phenotypesAnxiety : Modulation of anxiety-like behaviorsStress Response : Involvement in stress-related behaviorsTreatment Response : Potential for GALR1-targeted antidepressants
Pain Modulation : Galanin has analgesic propertiesFood Intake : Regulation of appetite and metabolismSleep-Wake Cycle : Modulates arousal states
GALR1 is a target for several therapeutic approaches:
Small Molecule Agonists : Blood-brain barrier penetrant galanin analogsPeptide Analogs : Modified galanin sequences with enhanced stabilityAllosteric Modulators : Subtype-selective positive allosteric modulatorsSignal-Biased Agonists : Favor neuroprotective pathways
Disorder
Approach
Status
AD
GALR1 agonists
Preclinical
Epilepsy
GALR1 agonists
Preclinical
Depression
GALR1 antagonists
Research
Neuropathic Pain
GALR1 agonists
Phase I
Agonists : Galanin, Galnon, [D-Trp²]-galanin(2-13)Antagonists : M35, C7, SNAP 37889Transgenic Mice : Galr1 knockout mice availableRadioligands : [^125I]-galanin for binding studies
GAL — Galanin neuropeptideGALR2 — Galanin Receptor 2GALR3 — Galanin Receptor 3NPY — Neuropeptide Y (related system)