Advanced glycosylation end product-specific receptor (RAGE) pre-messenger RNA (RAGE pre-mRNA)

Advanced glycosylation end product-specific receptor (RAGE) pre-messenger RNA is the primary transcript of the AGER gene, which encodes a multi-ligand cell surface receptor (UniProt: Q15109). RAGE is a member of the immunoglobulin superfamily and plays a critical role in the innate immune response and chronic inflammation by binding ligands such as advanced glycation end-products (AGEs), HMGB1, and S100/calgranulins (PubMed: 28232334). The pre-mRNA undergoes alternative splicing to generate different isoforms, most notably the full-length membrane-bound RAGE (mRAGE) and the soluble RAGE (sRAGE), which lacks the transmembrane domain (PubMed: 18061513). In pathological states like diabetes and Alzheimer's disease, the signaling through mRAGE is often upregulated, leading to chronic inflammation and tissue damage. Therapeutic targeting of RAGE pre-mRNA typically involves the use of antisense oligonucleotides (ASOs) to redirect splicing, promoting the inclusion or exclusion of specific exons to increase sRAGE production. By increasing sRAGE, which acts as a decoy receptor, the pro-inflammatory signaling of mRAGE is competitively inhibited. This approach provides a therapeutic avenue for conditions like Alzheimer's disease, diabetic nephropathy, and atherosclerosis by neutralizing circulating ligands before they can activate the membrane receptor (PubMed: 22535010). Current research focuses on optimizing the delivery of these splice-switching oligonucleotides to target tissues like the brain or kidneys.

Other names

AGER pre-mRNAReceptor for advanced glycation end-products pre-mRNAAdvanced glycation end product-specific receptor pre-mRNA

Modulation of alternative splicing to increase the ratio of soluble RAGE (sRAGE) to membrane-bound RAGE (mRAGE), thereby creating a decoy receptor to sequester pro-inflammatory ligands.