Related Experiment Video
Updated: May 29, 2025
07:41
A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
8.8K
GDF15 Analogues Acting as GFRAL Ligands
Andrea Di Santo1, Livio Tarchi2, Gianluca Villa3
1Department of Neuroscience, Psychology, Pharmacology and Infant Health, Interdepartmental Research Unit of Peptide and Protein Chemistry and Biology, University of, Florence, Via Ugo Schiff, 6, Sesto Fiorentino, FI, 50019, Italy.
Chemmedchem
|February 5, 2025
Summary
Growth Differentiation Factor 15 (GDF15) and its receptor GFRAL are key in energy balance and appetite. Targeting this pathway offers new treatments for obesity and cancer-related wasting.
Area of Science:
- Endocrinology
- Molecular Biology
- Physiology
Background:
- Growth Differentiation Factor 15 (GDF15) is a cytokine in the TGF-β superfamily with diverse physiological and pathological roles.
- Circulating GDF15 levels increase in various conditions, including aging, pregnancy, cancer, cardiovascular disease, and infections.
- GDF15 exerts effects like anorexia and cachexia primarily via the GFRAL receptor in the brainstem, involving RET co-receptor signaling for energy homeostasis and nausea.
Purpose of the Study:
- To review recent advancements in understanding GDF15-GFRAL signaling.
- To summarize bioactive GDF15-derived molecules and their pharmacological applications.
- To explore therapeutic strategies targeting the GDF15-GFRAL pathway for conditions like obesity and cancer cachexia.
Main Methods:
- Literature review of studies on GDF15-GFRAL signaling.
- Analysis of recent findings on GFRAL distribution and GDF15's broader roles.
- Summary of therapeutic approaches utilizing GDF15 analogues and peptides.
Main Results:
- GDF15-GFRAL signaling is central to energy homeostasis and nausea induction.
- Broader GFRAL distribution suggests diverse GDF15 functions.
- Two therapeutic strategies are emerging: GDF15 analogues as GFRAL agonists for obesity and GDF15 antagonists for cachexia.
Conclusions:
- The GDF15-GFRAL pathway presents significant therapeutic potential.
- Targeting this pathway could lead to novel treatments for obesity, cancer cachexia, and related disorders.
- Further research into GDF15-associated conditions and their treatment is warranted.
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