New Implications for the Role for Ubiquilin-1 in Molecular Mechanisms of Alzheime's Disease: Interrelationship with BACE1
Received Date: Jul 01, 2017 / Accepted Date: Aug 23, 2017 / Published Date: Aug 30, 2017
Abstract
Ample evidence links ubiquilins to the pathogenesis of various neurodegenerative disorders. Ubiquilin-1 (also called PLIC-1) is associated to the pathogenesis of Alzheimer’s disease (AD) both genetically and functionally as indicated by investigations in different in vitro and in vivo models and human brain. Previous studies by us and others have identified ubiquilin-1 as a central regulator of the metabolism, subcellular localization, trafficking, as well as accumulation and degradation of various neurodegenerative disease-linked proteins, including the AD-associated β-amyloid precursor protein (APP) and presenilins. Our recent report reveals a previously uncharacterized relationship between ubiquilin-1 and AD-associated β-site cleaving enzyme 1 (BACE1), the rate-limiting enzyme in the generation of the β-amyloid (Aβ) peptides, in cell-based model systems in vitro as well as in the brains of AD model mice in vivo and human patients. Our data suggest that ubiquilin-1 controls BACE1 levels and localization to the late endosomal compartment, the preferred cellular site for Aβ generation. Therefore, the observed decreased levels of ubiquilin-1 in AD brain may result in altered APP processing and Aβ accumulation. Here, we provide a short review on the links between ubiquilin-1 and mechanisms of AD and some other neurodegenerative diseases and then summarize the data in our recent report regarding the newly observed interrelationship between ubiquilin-1 and BACE1.
Keywords: Alzheimer’s disease; Ubiquilin-1; BACE1; Beta-amyloid; Ubiquitin-proteasome system; Autophagosome-lysosome pathway; Neurodegeneration
Citation: Takalo M, Natunen T, Leskelä S, Paldanius KMA, Soininen H, et al. (2017) New Implications for the Role for Ubiquilin-1 in Molecular Mechanisms of Alzheimer’s Disease: Interrelationship with BACE1. J Alzheimers Dis Parkinsonism 7: 365 Doi: 10.4172/2161-0460.1000365
Copyright: © 2017 Takalo M, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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