ABSTRACT
metabolism may not depend on cholinesterase inhibition Recent data demonstrate that the effect of ChEI on Ab metabolism does not necessarily relate to ChE inhibition.67,68 Phenserine, a carbamate-type of ChEI, reduces b-APP levels in vivo and also decreases secretion of soluble b-APP and Ab into the conditioned media of human neuroblastoma cells. However, phenserine action is neither mediated through a classical receptor signaling pathway, involving extracellular signal-regulated kinase or phosphatidylinositol 3kinase activation, nor is it associated with ChE inhibition. Phenserine reduces Ab levels by regulating b-APP translation by a putative interleukin-1 or TGF-b responsive element located within the 5-UTR.68 This effect is translated in the cortex of transgenic mice (APPswe PSI) with a 53% reduction of Ab1-42, which is evident following a 3-week treatment with phenserine.67,68 These results suggest that phenserine regulates APP protein expression at the post-transcriptional level, as it suppresses APP protein expression without altering message levels.
