title: Developing BACE-1 inhibitors for FXS.
abstract: Fragile X syndrome (FXS) is a debilitating genetic disorder with no cure and few therapeutic options. Excessive signaling through metabotropic glutamate receptor 5 in FXS leads to increased translation of numerous synaptic proteins and exaggerated long-term depression. Two of the overexpressed proteins are amyloid-beta protein precursor (APP) and its metabolite amyloid-beta, which have been well-studied in Alzheimer's disease (AD). Here we discus the possibility that pharmaceuticals under study for the modulation of these proteins in AD might be viable therapeutic strategies for FXS. Specifically, a recently identified acetyltransferase inhibitor that reduces the levels and activity of β-site APP cleaving enzyme (BACE-1) has strong potential to attenuate BACE-1 activity and maintain homeostatic levels APP catabolites in FXS.
authors.affiliation: Department of Neurology, University of Wisconsin Madison, WI, USA.
authors.forename: Cara J
authors.initials: CJ
authors.lastname: Westmark
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Chrysanthy
authors.initials: C
authors.lastname: Ikonomidou
authors.forename: Jerry C P
authors.initials: JC
authors.lastname: Yin
authors.forename: Luigi
authors.initials: L
authors.lastname: Puglielli
keywords: Alzheimer’s disease; BACE-1; amyloid-beta; fragile X syndrome; mGluR5