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
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..View full abstract
Awarded by National Health and Medical Research Council of Australia
Awarded by Australian Research Council
This work was supported by the National Health and Medical Research Council of Australia [grant number APP1082600]; and the Australian Research Council [grant number DP130103207].