title: Golgi defects enhance APP amyloidogenic processing in Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Gunjan
authors.initials: G
authors.lastname: Joshi
authors.forename: Yanzhuang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D016564:Amyloid beta-Protein Precursor
keywords: Alzheimer's disease; GRASP55; GRASP65; Golgi defects; amyloid beta; amyloid precursor protein; neuronal function