Journal article

Dysregulation of intracellular trafficking and endosomal sorting in Alzheimer's disease: controversies and unanswered questions

Wei Hong Toh, Paul A Gleeson

BIOCHEMICAL JOURNAL | PORTLAND PRESS LTD | Published : 2016

Abstract

Alzheimer's disease (AD) is characterized by the accumulation of amyloid plaques in the brain consisting of an aggregated form of amyloid β-peptide (Aβ) derived from sequential amyloidogenic processing of the amyloid precursor protein (APP) by membrane-bound proteases β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase. The initial processing of APP by BACE1 is re-gulated by intracellular sorting events of the enzyme, which is a prime target for therapeutic intervention. GWAS (genome-wide sequencing studies) have identified several AD-susceptibility genes that are associated with the regulation of membrane trafficking, and substantial evidence now indicates that AD is likely to arise from d..

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