D-Ribose Induces Cellular Protein Glycation and Impairs Mouse Spatial Cognition

BACKGROUND: D-ribose, an important reducing monosaccharide, is highly active in the glycation of proteins, and results in the rapid production of advanced glycation end products (AGEs) in vitro. However, whether D-ribose participates in glycation and leads to production of AGEs in vivo still requires investigation. METHODOLOGY/PRINCIPAL FINDINGS: Here we treated cultured cells and mice with D-ribose and D-glucose to compare ribosylation and glucosylation for production of AGEs. Treatment with D-ribose decreased cell viability and induced more AGE accumulation in cells. C57BL/6J mice intraperitoneally injected with D-ribose for 30 days showed high blood levels of glycated proteins and AGEs. Administration of high doses D-ribose also accelerated AGE formation in the mouse brain and induced impairment of spatial learning and memory ability according to the performance in Morris water maze test. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that D-ribose but not D-glucose reacts rapidly with proteins and produces significant amounts of AGEs in both cultured cells and the mouse brain, leading to accumulation of AGEs which may impair mouse spatial cognition

Inhibitors of JmjC-containing histone demethylases

Histone demethylases (KDMs) catalyse the removal of N-methyl marks on histones and play important roles in epigenetic regulation. Abnormal histone methylation and dysregulation of KDMs have been linked to multiple diseases, and KDMs are emerging as promising therapeutic targets. This chapter provides an overview of JmjC-domain-containing KDMs (JmjC-KDMs), with a particular focus on recent advances in JmjC-KDM inhibitor development from a structural perspective