Work

BDNF alters β-cleavage of APP and subcellular distribution of BACE1

Year: 2026

Type: article

Abstract: BACE1 cleavage of APP generates amyloid-β, overproduction of which perturbs physiological function in the brain. The neurotrophic factor BDNF reduces BACE1 cleavage of APP, potentially reducing amyloid-β production in the brain. Here, we show that this may be the result of BDNF altering the subcellular distribution of BACE1, reducing localization to acidic compartments where enzymatic activity is increased. This effect is independent of clathrin-mediated endocytosis, as BACE1 cleavage of APP is unchanged by PitStop2 treatment.

Source: American Journal of Physiology-Cell Physiology

DOI: 10.1152/ajpcell.00642.2025

Authors: Ryan D. Hallam, Gregory Foran, Natasha K. Fletcher, Rebecca E. K. MacPherson, Aleksandar Necakov

Institutions: Western University, Brock University, Baylor College of Medicine

Language: English

Topic: Alzheimer's disease research and treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Funders: Natural Sciences and Engineering Research Council of Canada, RES’EAU-WaterNET