ISSN: 2161-0460

Journal of Alzheimers Disease & Parkinsonism
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  • Review Article   
  • J Alzheimers Dis Parkinsonism 2017, Vol 7(5): 365
  • DOI: 10.4172/2161-0460.1000365

New Implications for the Role for Ubiquilin-1 in Molecular Mechanisms of Alzheime's Disease: Interrelationship with BACE1

Mari Takalo1, Teemu Natunen1, Stina Leskelä2, Kaisa MA Paldanius1, Hilkka Soininen3,4, Mikko Hiltunen1,4 and Annakaisa Haapasalo2*
1Institute of Biomedicine, University of Eastern Finland, Yliopistonranta 1E, 70211 Kuopio, Finland
2A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, 70211 Kuopio, Finland
3Institute of Clinical Medicine-Neurology, , Yliopistonranta 1C, 70211 Kuopio, Finland
4NeuroCenter, Neurology, , Kuopio University Hospital, P.O. Box 100, 70029, Kuopio, Finland
*Corresponding Author : Annakaisa Haapasalo, Associate Professor, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2,70211 Kuopio, Finland, Tel: +358 40 355 2768, Fax: +358 17 163 539, Email: annakaisa.haapasalo@uef.fi

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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