RAGEactiviteit

RAGEactiviteit refers to the activity of the receptor for advanced glycation end products (RAGE), a pattern recognition receptor that responds to diverse ligands and modulates inflammatory and oxidative stress signaling.

RAGE belongs to the immunoglobulin superfamily; upon ligand binding, it activates intracellular signaling pathways such as NF-kB, MAPKs, and JAK/STAT, leading to transcription of proinflammatory genes and reactive oxygen species production.

RAGE ligands include advanced glycation end products (AGEs), HMGB1, members of the S100 protein family (notably S100A8/A9 and S100B), and amyloid-beta. RAGE is expressed in many tissues, with high levels in the lungs, vasculature, neurons and immune cells.

Clinically, increased RAGE activity is linked to chronic inflammatory and degenerative conditions, including diabetic complications (nephropathy, retinopathy), cardiovascular disease, COPD, rheumatoid arthritis, and neurodegenerative diseases such as Alzheimer's disease. The balance with soluble RAGE (sRAGE), which can act as a decoy receptor, modulates signaling and is studied as a biomarker.

Therapeutically, strategies aim to reduce RAGE activation or block ligand binding; approaches include decoy receptors (sRAGE), antibodies, and small-molecule antagonists. Notable drugs/treatments include FPS-ZM1 (a preclinical inhibitor) and Azeliragon (TTP488), which reached Phase III for Alzheimer's but was not successful in efficacy trials.

Research status: RAGEactiviteit remains an active area of investigation, with ongoing studies to clarify causal roles in disease and to identify safe, effective inhibitors. Measurement commonly uses RAGE expression, circulating sRAGE levels, or downstream signaling markers.