Potential therapeutic targets within trained immunity pathways in gout
| No. | Category | Modulator | Mechanism of action |
|---|---|---|---|
| 1 | Cytokine targeting therapies | IL-1 inhibitors (e.g., anakinra, canakinumab) | Neutralize IL-1β, preventing trained monocyte/macrophage hyperactivity [41, 42] |
| 2 | Inflammasome inhibitors | NLRP3 inhibitors (e.g., MCC950, OLT1177) | Prevent NLRP3 inflammasome assembly, reducing IL-1β secretion [43, 44, 46, 47] |
| 3 | Metabolic modulators | AMPK activators (e.g., metformin, AICAR) | Activate AMPK, shifting metabolism away from inflammatory glycolysis [38] |
| 4 | mTOR inhibitors (e.g., rapamycin, everolimus) | Inhibit mTOR signaling, suppressing glycolysis-dependent immune activation [58, 59] | |
| 5 | Statins (e.g., atorvastatin, simvastatin) | Reduce mevalonate pathway flux, disrupting monocyte/macrophage training [61, 64] | |
| 6 | Epigenetic modulators | DNMT inhibitors (e.g., 5-azacytidine; α-ketoglutarate) | Inhibit DNA methylation, reversing epigenetic priming in monocytes [71, 72] |
| 7 | HDAC inhibitors (e.g., vorinostat, panobinostat) | Suppress histone deacetylation, reducing inflammatory gene expression [81–83] | |
| 8 | LncRNA modulators | HOTAIR (HOX transcript antisense RNA) inhibitors | Regulates chromatin remodeling, influencing inflammatory gene expression in trained monocytes [87] |
| 9 | SNHG8 (small nucleolar RNA host gene 8) modulators | Modulates metabolic pathways involved in monocyte activation and cytokine production [88] | |
| 10 | Non-nucleoside DNMT1 inhibitor | RG108 | Restores normal DNA methylation by inhibiting DNMTs, reducing oxidative stress-induced damage [97] |
IL-1: interleukin-1; mTOR: mechanistic target of rapamycin; lncRNA: long non-coding RNA; DNMT: DNA methyltransferase; NLRP3: NACHT, LRR, and PYD domains-containing protein 3; HDAC: histone deacetylase
OIG: Conceptualization, Writing—original draft. LABJ: Conceptualization, Writing—review & editing, Funding acquisition. TOC: Conceptualization, Writing—review & editing, Funding acquisition.
The authors declare no competing interests.
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This work was supported by a Romania’s National Recovery and Resilience Plan grant of the Romanian Ministry of Investments and European Projects [PNRR-III-C9-2022-I8, CF 85/15.11.2022]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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