GAL Human
Description
Receptor Interactions and Signaling
Galanin binds to three G protein-coupled receptors (GPCRs): GALR1, GALR2, and GALR3, each with distinct roles .
Receptor Distribution and Function
| Receptor | Primary Locations | Key Functions |
|---|---|---|
| GALR1 | Brain (hypothalamus, cortex), pancreas | Modulates anxiety, cognition, insulin secretion |
| GALR2 | Brain (ventral forebrain), gastrointestinal tract | Regulates mood, appetite, neuroprotection |
| GALR3 | Brain (amygdala), peripheral tissues | Linked to neurogenesis and addiction |
GALR2 is of particular interest due to its therapeutic potential. Mutagenesis studies identified residues (Gln5→Asn, Met7→Ala, Lys11→Phe, Ala13→Pro) in spexin (SPX), a GALR2/GALR3 agonist, that enhance GALR2 specificity while abolishing GALR1/GALR3 activity .
Physiological Roles and Disease Associations
Galanin’s inhibitory effects on neurotransmitter release underpin its roles in:
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Neuroprotection: Upregulated during axotomy or seizures, promoting neuronal survival .
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Cognitive Regulation: Modulates memory and learning via interactions with acetylcholine and serotonin .
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Mood and Appetite: GALR2 activation reduces stress and anxiety .
Pathological Implications
GALR2-Specific Agonists
Quadruple mutants of SPX (e.g., Q5N, M7A, K11F, A13P) show nanomolar potency for GALR2 without activating GALR1/GALR3 . These agonists may treat anxiety and depression.
| Mutant SPX | GALR2 EC₅₀ (nM) | GALR3 EC₅₀ (nM) |
|---|---|---|
| Wild-type | 2.1 | 15.3 |
| Quadruple | 2.8 | >10,000 |
Data from receptor activation assays .
GAL-101: A Neuroprotective Agent
While not directly related to galanin, GAL-101 (a misfolded amyloid-β binder) highlights therapeutic strategies in neurodegeneration. It prevents oligomerization by promoting inert "clusters," reducing retinal amyloid-β in models of dry AMD and glaucoma .
Challenges and Future Directions
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Species-Specific Effects: Porcine GAL lacks efficacy in humans, emphasizing the need for autologous studies .
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GALR3 Complexity: Limited data on GALR3’s role in addiction and neurogenesis warrants further exploration .
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Clinical Translation: GALR2 agonists require optimization for CNS penetration and metabolic stability .
Product Specs
Q&A
FAQs for Researchers on GAL Human (Galanin & Anti-Gal Antibody)
Advanced Research Questions
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What mechanisms link anti-Gal antibodies to autoimmune pathologies like Graves’ disease?
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How can peptide engineering overcome challenges in developing GALR2-specific agonists?
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Strategy: Substitute SPX1 residues with GAL-specific motifs (e.g., Trp2, Tyr9) to enhance receptor specificity. For example:
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Functional Validation:
Receptor Signaling Pathway SPX1 Mutant Efficacy GALR2 Gq-coupled High (EC₅₀ ~50 nM) GALR3 Gi-coupled Low/no activation -
Limitation: Off-target effects on GALR1 require rigorous selectivity screening .
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Methodological Challenges
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How do bacterial α-galactosyl epitopes confound in vitro studies of anti-Gal interactions?
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What epigenetic factors influence GAL dysregulation in cancer models?
Data Interpretation Guidelines
Product Science Overview
Galanin prepropeptide is a neuroendocrine peptide widely expressed in the central and peripheral nervous systems, as well as in various other tissues such as the gastrointestinal tract, pancreas, adrenal gland, and urogenital tract . The human recombinant form of this peptide is used in research to study its physiological functions and potential therapeutic applications.
The gene encoding galanin prepropeptide is known as the GAL gene . This gene produces a precursor protein that is proteolytically processed to generate two mature peptides: galanin and galanin message-associated peptide (GMAP) . Galanin is a small neuropeptide that binds and activates G protein-coupled receptors (GPCRs), specifically GALR1, GALR2, and GALR3 .
Galanin has diverse physiological functions, including:
- Nociception: It plays a role in the perception of pain.
- Feeding and Energy Homeostasis: It is involved in regulating appetite and energy balance.
- Osmotic Regulation and Water Balance: It helps maintain fluid balance in the body .
GMAP, on the other hand, has been demonstrated to possess antifungal activity and is hypothesized to be part of the innate immune system .
Galanin exerts its effects by binding to its receptors, GALR1, GALR2, and GALR3, which are G protein-coupled receptors . These receptors are involved in various signaling pathways, including GPCR downstream signaling and Class A/1 (Rhodopsin-like receptors) . The binding of galanin to these receptors can regulate diverse physiological functions, such as the contraction of smooth muscle in the gastrointestinal and genitourinary tracts, growth hormone and insulin release, and adrenal secretion .
The study of galanin and its receptors has significant implications for understanding and treating various diseases. For example, galanin receptors are being investigated as potential targets for treating conditions such as Alzheimer’s disease, anxiety, and addiction . The structural analysis of galanin receptors, such as GALR2, provides insights into ligand specificity and assists in structure-based drug design .
