Carbonyl reductase [NADPH] 1

Carbonyl reductase [NADPH] 1 (CBR1) is an NADPH-dependent reductase with broad substrate specificity that catalyzes the reduction of diverse carbonyl compounds including quinones, prostaglandins, menadione, and xenobiotics (UniProt: P16152). It is notable for converting anthracycline antitumor drugs such as doxorubicin to cardiotoxic metabolites, and participates in glucocorticoid metabolism by reducing cortisol and corticosterone to weakly active steroid metabolites in adipose tissue. CBR1 can also reduce S-nitrosoglutathione and bind glutathione-conjugated substrates.

CBR1 is broadly expressed with established roles in drug metabolism and steroid hormone inactivation. No disease associations are annotated in the UniProt record, though the enzyme's involvement in oxidative stress responses through nitrosoglutathione reduction suggests potential relevance to inflammatory or degenerative pathways (UniProt: P16152).

CBR1 is significantly upregulated in Alzheimer's Disease brain tissue, with a mean log2 fold-change of 0.95 in post-mortem AD samples compared to age-matched controls (Chaparral AD proteomics). This elevation may reflect altered metabolic demands or compensatory responses to oxidative stress in the degenerating AD brain, though the functional consequence of increased CBR1 abundance in AD pathology remains to be determined.