The neuronal-specific isoform of BIN1 regulates β-secretase cleavage of APP and Aβ generation in a RIN3-dependent manner.

ABSTRACT: Genome-wide association studies have identified BIN1 (Bridging integrator 1) and RIN3 (Ras and Rab interactor 3) as genetic risk factors for late-onset Alzheimer's disease (LOAD). The neuronal isoform of BIN1 (BIN1V1), but not the non-neuronal isoform (BIN1V9), has been shown to regulate tau-pathology and Aβ generation via RAB5-mediated endocytosis in neurons. BIN1 directly interacts with RIN3 to initiate RAB5-mediated endocytosis, which is essential for β-secretase (BACE1)-mediated β-secretase cleavage of β-amyloid precursor protein (APP) to generate Amyloid-β (Aβ), the key component of senile plaques in AD. Understanding the regulatory roles of BIN1 (neuronal BIN1V1) and RIN3 in β-secretase mediated cleavage of APP and Aβ generation is key to developing novel therapeutics to delay or pre

SUBMITTER: Bhattacharyya R 

PROVIDER: S-EPMC8894474 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature