(i) HNE is a RCS that damages proteins at various amino acid residues to form either a Schiff base or a Michael adduct. (ii) HNE can be detoxified through natural defense mechanisms including aldehyde dehydrogenases or glutathione transferases, which create a stable product that is exported out of cells and cleared by renal mechanisms. (iii) Left: HNE can also be sequestered by carnosine, creating a stable HNE-carnosine adduct that is nonreactive. However, carnosine is degraded by carnosinases, which limit HNE sequestration in vivo. Right: To circumvent carnosine degradation via carnosinases, a next-generation carnosine derivative called carnosinol was created, which is resistant to carnosinase degradation and has strong affinity for RSC.