BACE1 Inhibitor MK-8931 Alters Formation but Not Stability of Dendritic Spines.

ABSTRACT: Beta-site amyloid-precursor-protein cleaving enzyme 1 (BACE1) is the rate limiting protease in the production of the amyloid-beta peptide (Aβ), which is considered to be the causative agent in the pathogenesis of Alzheimer's Disease (AD). Therefore, the therapeutic potential of pharmacological BACE1 inhibitors is currently tested in clinical trials for AD treatment. To ensure a positive clinical outcome it is crucial to identify and evaluate adverse effects associated with BACE1 inhibition. Preclinical studies show that chronic blockade of BACE1 activity alters synaptic functions and leads to loss of dendritic spines. To assess the mechanism of synapse loss, dendritic spine dynamics of pyramidal layer V cells were monitored by in vivo two-photon microscopy in the somatosensory corte

SUBMITTER: Blume T 

PROVIDER: S-EPMC6070607 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature