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Phospholipase A2 group X (PLA2G10)
- Target
- PLA2G10
- Molecular classification
- Enzyme, Secreted phospholipase A2 (sPLA2), Lipid metabolism enzyme
01
Overview
Phospholipase A2 group X (PLA2G10) is a member of the secreted phospholipase A2 family of calcium-dependent enzymes that hydrolyze membrane glycerophospholipids to release free fatty acids, such as arachidonic acid, and lysophospholipids. These lipid mediators are central to the generation of bioactive compounds involved in inflammation, immune responses, and host defense. PLA2G10 is especially potent in releasing arachidonic acid from membrane phospholipids and is implicated in diverse processes including inflammatory diseases (such as asthma and atherosclerosis), host defense against pathogens, and the modulation of tumor microenvironments through effects on immune cell infiltration. Elevated or dysregulated expression is observed in cancer, cardiovascular and allergic diseases, and its activity is a focus for therapeutic development, though non-selective inhibition poses clinical risks due to the enzyme’s complex roles in both disease and homeostasis.
- Other names
- Group 10 secretory phospholipase A2sPLA2-XGX sPLA2GXPLA2Phosphatidylcholine 2-acylhydrolase 10PA2GXGroup X secretory phospholipase A2
02
Mechanism of action
Inhibitors block sPLA2 enzymatic activity, preventing hydrolysis of membrane phospholipids and the downstream production of pro-inflammatory lipid mediators such as prostaglandins and leukotrienes
03
Biological functions
Hydrolysis of glycerophospholipids to free fatty acids and lysophospholipidsRelease of arachidonic acid and production of pro-inflammatory lipid mediators such as prostaglandins and cysteinyl leukotrienesRegulation of inflammatory responses and immune cell activationRegulation of stem cell niches, differentiation (such as colon/intestinal epithelial cells), and host defense against bacteria and virusesRegulation of eosinophil activation and leukotriene synthesis (implications in asthma and allergy)Modulation of tumor microenvironment (impacts T cell infiltration in cancer)
04
Disease associations
Cancer (especially tumor immune evasion and proliferation)InflammationCardiovascular disease (atherosclerosis)Asthma and allergic diseasesInfectious diseases (bacterial and viral defense)Obesity and lipid metabolism disordersAcute respiratory distress syndromeSickle cell disease (association)
05
Safety considerations
Non-selective inhibition of sPLA2 enzymes (e.g., by varespladib) can disrupt both pro- and anti-atherogenic actions, potentially worsening cardiovascular outcomesInhibition might impair host defense mechanisms or homeostatic immune responses
06
Interacting drugs
Varespladib (A-002), a non-specific sPLA2 inhibitor investigated for atherosclerosis and coronary artery disease
1 more in the full profile.
07
Biomarkers
Expression of PLA2G10 may serve as a biomarker in some cancers (colorectal cancer, for both progression and immune cell infiltration)PLA2G10 expression/activity linked to inflammatory conditions (asthma, allergy)Potential marker for adverse prognosis in cardiovascular disease and response to anti-inflammatory strategies
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