Golgi defects enhance APP amyloidogenic processing in Alzheimer's disease

G Joshi, Y Wang - Bioessays, 2015 - Wiley Online Library
Bioessays, 2015Wiley Online Library
Increased amyloid beta (Aβ) production by sequential cleavage of the amyloid precursor
protein (APP) by the β‐and γ‐secretases contributes to the etiological basis of Alzheimer's
disease (AD). This process requires APP and the secretases to be in the same subcellular
compartments, such as the endosomes. Since all membrane organelles in the
endomembrane system are kinetically and functionally linked, any defects in the trafficking
and sorting machinery would be expected to change the functional properties of the whole …
Increased amyloid beta (Aβ) production by sequential cleavage of the amyloid precursor protein (APP) by the β‐ and γ‐secretases contributes to the etiological basis of Alzheimer's disease (AD). This process requires APP and the secretases to be in the same subcellular compartments, such as the endosomes. Since all membrane organelles in the endomembrane system are kinetically and functionally linked, any defects in the trafficking and sorting machinery would be expected to change the functional properties of the whole system. The Golgi is a primary organelle for protein trafficking, sorting and modifications, and Golgi defects have been reported in AD. Here we hypothesize that Golgi fragmentation in AD accelerates APP trafficking and Aβ production. Furthermore, Golgi defects may perturb the proper trafficking and processing of many essential neuronal proteins, resulting in compromised neuronal function. Therefore, molecular tools that can restore Golgi structure and function could prove useful as potential drugs for AD treatment.
Wiley Online Library