Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and a decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play a central role in AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, is axonally transported in neurons and accumulates in dystrophic neurites near cerebral amyloid deposits in AD. BACE1 is modified by S-palmitoylation at four juxtamembrane cysteine residues. S-palmitoylation is a dynamic posttranslational modification that is important for trafficking and function of several synaptic proteins. Here, we investigated the in vivo significance of BACE1 S-palmitoylation throug

SUBMITTER: Andrew RJ 

PROVIDER: S-EPMC5692556 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature