Melatonin regulates the transcription of βAPP-cleaving secretases mediated through melatonin receptors in human neuroblastoma SH-SY5Y cells.

摘要: Melatonin is involved in the control of various physiological functions, such as sleep, cell growth and free radical scavenging. The ability melatonin to behave an antioxidant, together with fact that Alzheimer-related amyloid β-peptide (Aβ) triggers oxidative stress through hydroxyl radical-induced death, suggests could reduce Alzheimer's pathology. Although exact etiology disease (AD) remains be established, excess Aβ believed primary contributor dysfunction degeneration neurons occurs AD. peptides are produced via sequential cleavage β-secretase β-site APP-cleaving enzyme 1 (BACE1) γ-secretase (PS1/PS2), while α-secretase (ADAM10) prevents production peptides. We hypothesized inhibit BACE1 PS1/PS2 enhance ADAM10 expression. Using human neuronal SH-SY5Y line, we found inhibited PS1 activated mRNA level protein expression a concentration-dependent manner mediated G protein-coupled receptors. inhibits expressions attenuation nuclear factor-κB phosphorylation (pNF-κB). Moreover, reduced promoter transactivation consequently downregulated catalytic activity. present data show not only potential regulator β/γ-secretase but also activator activation kinase C, thereby favoring nonamyloidogenic pathway over amyloidogenic pathway. Altogether, our findings suggest may therapeutic agent for reducing risk AD humans.