51ºÚÁϳԹÏÍø

Abstract

The aspartyl protease β-site AβPP-cleaving enzyme 1 (BACE1) catalyzes the rate-limiting step in Aβ production, a peptide at the nexus of neurodegenerative cascades in Alzheimer Disease dementia. Leptin may offer protection against Alzheimer�s dementia as this adipocytokine can reduce Aβ production and decrease BACE1 activity and expression levels. However, the signaling cascades involved in the leptin-induced mitigation in Aβ levels and BACE1 expression levels have not been elucidated. We have demonstrated that NF-κB positively regulates BACE1 transcription. NF-κB activity is tightly regulated by the mammalian sirtuin SIRT1. Multiple studies have cogently evinced that leptin activates the metabolic master regulator SIRT1. In this study, we determined the extent to which SIRT1 expression and activity regulate the leptin-induced attenuation in BACE1 expression and Aβ levels. This study also elucidated and delineated the signal transduction pathways involved in the leptin induced mitigation in BACE1 expression.

Biography

Othman Ghribi has completed his Ph.D. in 1994 at the University Ren� Descartes, Partis France, and postdoctoral studies from the University of Quebec and the University of Virginia. He has published more than 60 papers in reputed journals and serving as a Senior Editor of The Journal of Alzheimer�s Disease and is a member on the editorial board of the Journal of Alzheimer�s Disease and Parkinsonism, American Journal of Neurodegenerative Diseases, and Current Alzheimer Research.