Abstract

Objective. Advanced glycation end products (AGEs) and their mRAGE receptor play an important role in the pathogenesis of metabolic diseases. AGEs modify proteins and interact with RAGE with subsequent activation of various signaling pathways, including induction of oxidative stress and resulting activation of nuclear factor kappa-B with subsequent inflammatory response. AGE-RAGE axis, along with other mechanisms, is involved in the pathogenesis of later diabetic complications.

Results and discussion. The role of RAGE in various clinical situations is currently being intensively studied. AGEs and RAGE alone do not appear to serve as a universal biomarker. On the other hand, the soluble AGEs receptor (sRAGE) neutralizes unwanted interactions by competitive binding with AGEs and may be a potential protective factor in the development of some diseases. Low levels of sRAGE have been suggested as a biomarker of diseases other than diabetes mellitus and kidney disease (where sRAGE levels are elevated). Circulating sRAGE levels can be increased or even decreased in various diseases while increasing AGE levels. sRAGE can serve as a biomarker of disease incidence and adverse symptoms or as a prognostic biomarker of irreversible homeostasis or mortality.

Conclusion. It seems practical to evaluate the so-called AGE-RAGE stress as the ratio of measured circulating AGE/sRAGE levels. An increased AGEs/sRAGE ratio may be a universal or risk biomarker. Based on promising experimental results, mRAGE alone may be a therapeutic target in some diseases (Tab. 7, Fig. 4, Ref. 148). Text in PDF www.lekarskyobzor.sk.

KEY WORDS: AGEs, RAGE, metabolic, inflammation and autoimmunity diseases, oxidative stress, cancer, COVID-19, aging, senescence.

Lek Obz 2022, 71 (11): 498-511

Vladimír JAKUŠ 1, Rastislav EDELSTEIN 2, Marián BERNADIČ 3, Ľubomír KURAČKA 1, Jana MUCHOVÁ 1, Ladislav TURECKÝ 1

1 Ústav lekárskej chémie, biochémie a klinickej biochémie, LF UK Bratislava, prednosta prof. MUDr. L. Turecký, CSc.
2 Klinika stomatológie a maxilofaciálnej chirurgie LF UK a OÚSA Bratislava, prednosta MUDr. B. Novák, PhD.
3 Ústav patologickej fyziológie LF UK Bratislava, prednosta prof. MUDr. F. Šimko, CSc., FECS

CITE
JAKUŠ V., EDELSTEIN R., BERNADIČ M. et al.: AGE-RAGE stress: the importance of AGE/sRAGE ratio studied in various diseases. Part I. General aspects. Lek Obz 2022, 71 (11): 498-511