BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and β-amyloid production in Alzheimer’s disease
1 Institut de Pharmacologie Moléculaire et Cellulaire, UMR7275 CNRS/UNSA, 06560, Valbonne, France
2 Team labelized Fondation pour la Recherche Médicale, 660 route des Lucioles, Sophia Antipolis, 06560, Valbonne, France
3 LABEX (Laboratory of Excellence), 660 route des Lucioles, Sophia Antipolis, 06560, Valbonne, France
Molecular Neurodegeneration 2012, 7:52 doi:10.1186/1750-1326-7-52Published: 5 October 2012
Alzheimer’s disease (AD) is a complex age-related pathology, the etiology of which has not been firmly delineated. Among various histological stigmata, AD-affected brains display several cellular dysfunctions reflecting enhanced oxidative stress, inflammation process and calcium homeostasis disturbance. Most of these alterations are directly or indirectly linked to amyloid β-peptides (Aβ), the production, molecular nature and biophysical properties of which likely conditions the degenerative process. It is particularly noticeable that, in a reverse control process, the above-described cellular dysfunctions alter Aβ peptides levels. β-secretase βAPP-cleaving enzyme 1 (BACE1) is a key molecular contributor of this cross-talk. This enzyme is responsible for the primary cleavage generating the N-terminus of “full length” Aβ peptides and is also transcriptionally induced by several cellular stresses. This review summarizes data linking brain insults to AD-like pathology and documents the key role of BACE1 at the cross-road of a vicious cycle contributing to Aβ production.