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Amyloid β production along the neuronal secretory pathway: Dangerous liaisons in the Golgi?
Author(s) -
Fourriere Lou,
Gleeson Paul A.
Publication year - 2021
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/tra.12808
Subject(s) - golgi apparatus , endosome , microbiology and biotechnology , biology , secretory pathway , amyloid precursor protein , amyloid precursor protein secretase , p3 peptide , intracellular , alzheimer's disease , disease , endoplasmic reticulum , pathology , medicine
β‐amyloid peptides (Aβ) are generated in intracellular compartments of neurons and secreted to form cytotoxic fibrils and plaques. Dysfunctional membrane trafficking contributes to aberrant Aβ production and Alzheimer's disease. Endosomes represent one of the major sites for Aβ production and recently the Golgi has re‐emerged also as a major location for amyloid precursor protein (APP) processing and Aβ production. Based on recent findings, here we propose that APP processing in the Golgi is finely tuned by segregating newly‐synthesised APP and the β‐secretase BACE1 within the Golgi and into distinct trans ‐Golgi network transport pathways. We hypothesise that there are multiple mechanisms responsible for segregating APP and BACE1 during transit through the Golgi, and that perturbation in Golgi morphology associated with Alzheimer's disease, and or changes in cholesterol metabolism associated with Alzheimer's disease risk factors, may lead to a loss of partitioning and enhanced Aβ production.