Facilitation of glutamate, but not GABA, release in Familial Alzheimer's APP mutant Knock-in rats with increased β-cleavage of APP.

ABSTRACT: Amyloid precursor protein (APP) modulates glutamate release via cytoplasmic and intravesicular interactions with the synaptic vesicle release machinery. The intravesicular domain, called ISVAID, contains the BACE1 cleavage site of APP. We have tested the functional significance of BACE1 processing of APP using App-Swedish (App^s ) knock-in rats, which carry an App mutation that causes familial Alzheimer's disease (FAD) in humans. We show that in App^s rats, β-cleavage of APP is favored over α-cleavage. App^s rats show facilitated glutamate, but not GABA, release. Our data support the notion that APP tunes glutamate release, and that BACE1 cleavage of the ISVAID segment of APP facilitates this function. We define this phenomenon as BACE1 on APP-dependent glutam

SUBMITTER: Tambini MD 

PROVIDER: S-EPMC6826143 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature