High glucose-mediated PICALM and mTORC1 modulate processing of amyloid precursor protein via endosomal abnormalities.

ABSTRACT:

Background and purpose

Although diabetes mellitus (DM) is an important risk factor for Alzheimer's disease (AD), the detailed mechanism(s) by which DM regulates amyloid β (Aβ) processing is still unclear. The longer residence time of amyloid precursor protein (APP) in endosomes is critical for Aβ production and DM is known to cause endosomal dysregulation. Here we have examined the effects of high glucose on APP-producing endosomes and related signaling pathways.

Experimental approach

To identify the underlying mechanisms, we investigated the effects of high glucose on abnormalities in early endosomes and related signalling pathways in human neuroblastoma cells. In vivo, diabetic mice treated with pharmacological inhibitors were used to examine endosomal dysfunction.

Key

SUBMITTER: Chae CW 

PROVIDER: S-EPMC7393198 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature