%0 Journal Article
%T BACE1 is at the crossroad of a toxic vicious cycle involving cellular stress and ¦Â-amyloid production in Alzheimer¡¯s disease
%A Chami Linda
%A Checler Fr¨¦d¨¦ric
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-52
%X 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 ¦Â-peptides (A¦Â), 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 A¦Â peptides levels. ¦Â-secretase ¦ÂAPP-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¡± A¦Â 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 A¦Â production.
%K Alzheimer¡¯s disease
%K BACE1
%K Inflammation
%K Oxidative stress
%K Calcium
%U http://www.molecularneurodegeneration.com/content/7/1/52