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- W1528787410 endingPage "347" @default.
- W1528787410 startingPage "329" @default.
- W1528787410 abstract "Alzheimer's disease (AD) affects almost 35 million people worldwide. One of the neuropathological features of AD is the presence of extracellular amyloid plaques, which are mainly composed of amyloid-β (Aβ) peptides. These peptides derive from the amyloidogenic proteolytic processing of the amyloid-β protein precursor (AβPP), through the sequential action of β- and γ-secretases. However, AβPP can also be cleaved by a non-amyloidogenic pathway, involving an α-secretase, and in this case the Aβ formation is precluded. The production of Aβ and of other AβPP catabolites depends on the spatial and temporal co-localization of AβPP with α- or β-secretases and γ-secretase, which traffic through the secretory pathway in a highly regulated manner. Disturbances on AβPP and secretases intracellular trafficking and, consequently, in their localization may affect dynamic interactions between these proteins with consequences in the AD pathogenesis. In this article, we critically review the recent knowledge about the trafficking and co-localization of AβPP and related secretases in the brain under physiological and AD conditions. A particular focus is given to data concerning the distribution of AβPP and secretases in different types of synapses relatively to other neuronal or glial localizations. Furthermore, we discuss some possible signals that govern the dynamic encounter of AβPP with each group of secretases, such as AβPP mutations, estrogen deprivation, chronic stress, metabolic impairment, and alterations in sleep pattern-associated with aging. The knowledge of key signals that are responsible for the shifting of AβPP processing away from α-secretases and toward the β-secretases might be useful to develop AD therapeutic strategies." @default.
- W1528787410 created "2016-06-24" @default.
- W1528787410 creator A5001293004 @default.
- W1528787410 creator A5058483077 @default.
- W1528787410 creator A5058867273 @default.
- W1528787410 creator A5085754928 @default.
- W1528787410 date "2015-03-18" @default.
- W1528787410 modified "2023-10-13" @default.
- W1528787410 title "Localization and Trafficking of Amyloid-β Protein Precursor and Secretases: Impact on Alzheimer's Disease" @default.
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