KUKU

KU ScholarWorks

  • myKU
  • Email
  • Enroll & Pay
  • KU Directory
    • Login
    View Item 
    •   KU ScholarWorks
    • Pharmacy, School of
    • Pharmacy Scholarly Works
    • View Item
    •   KU ScholarWorks
    • Pharmacy, School of
    • Pharmacy Scholarly Works
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Decreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer's Disease Brain Mitochondria

    Thumbnail
    View/Open
    YanShirley_JA_27(1)75.pdf (627.7Kb)
    Issue Date
    2011
    Author
    Alikhani, Nyosha
    Guo, Lan
    Yan, Shiqiang
    Du, Heng
    Pinho, Catarina Moreira
    Chen, John Xi
    Glaser, Elzbieta
    Yan, Shirley ShiDu
    Publisher
    IOS Press
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
    Metadata
    Show full item record
    Abstract
    Accumulation of amyloid-β peptide (Aβ), the neurotoxic peptide implicated in the pathogenesis of Alzheimer's disease (AD), has been shown in brain mitochondria of AD patients and of AD transgenic mouse models. The presence of Aβ in mitochondria leads to free radical generation and neuronal stress. Recently, we identified the presequence protease, PreP, localized in the mitochondrial matrix in mammalian mitochondria as the novel mitochondrial Aβ-degrading enzyme. In the present study, we examined PreP activity in the mitochondrial matrix of the human brain's temporal lobe, an area of the brain highly susceptible to Aβ accumulation and reactive oxygen species (ROS) production. We found significantly lower hPreP activity in AD brains compared with non-AD age-matched controls. By contrast, in the cerebellum, a brain region typically spared from Aβ accumulation, there was no significant difference in hPreP activity when comparing AD samples to non-AD controls. We also found significantly reduced PreP activity in the mitochondrial matrix of AD transgenic mouse brains (Tg mAβPP and Tg mAβPP/ABAD) when compared to non-transgenic aged-matched mice. Furthermore, mitochondrial fractions isolated from AD brains and Tg mAβPP mice had higher levels of 4-hydroxynonenal, an oxidative product, as compared with those from non-AD and nonTg mice. Accordingly, activity of cytochrome c oxidase was significantly reduced in the AD mitochondria. These findings suggest that decreased PreP proteolytic activity, possibly due to enhanced ROS production, contributes to Aβ accumulation in mitochondria leading to the mitochondrial toxicity and neuronal death that is exacerbated in AD. Clearance of mitochondrial Aβ by PreP may thus be of importance in the pathology of AD.
    Description
    This is the published version. Copyright 2011 by Journal of Alzheimer's Disease.
    URI
    http://hdl.handle.net/1808/17858
    DOI
    https://doi.org/10.3233/JAD-2011-101716
    Collections
    • Pharmacy Scholarly Works [286]
    Citation
    Alikhani, Nyosho, Lan Guo, Shiqiang Yan, Heng Du, Catarina Moreira Pinho, John Xi Chen, Elzbieta Glaser, and Shirley ShiDu Yan. "Decreased Proteolytic Activity of the Mitochondrial Amyloid-β Degrading Enzyme, PreP Peptidasome, in Alzheimer's Disease Brain Mitochondria." Journal of Alzheimer's Disease 27.1 (2011): 75-87. Iospresss. Web. 28 May 2015. http://dx.doi.org/10.3233/JAD-2011-101716.

    Items in KU ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.


    We want to hear from you! Please share your stories about how Open Access to this item benefits YOU.


    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    Browse

    All of KU ScholarWorksCommunities & CollectionsThis Collection

    My Account

    LoginRegister

    Statistics

    View Usage Statistics

    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

    The University of Kansas
      Contact KU ScholarWorks
    Lawrence, KS | Maps
     
    • Academics
    • Admission
    • Alumni
    • Athletics
    • Campuses
    • Giving
    • Jobs

    The University of Kansas prohibits discrimination on the basis of race, color, ethnicity, religion, sex, national origin, age, ancestry, disability, status as a veteran, sexual orientation, marital status, parental status, gender identity, gender expression and genetic information in the University’s programs and activities. The following person has been designated to handle inquiries regarding the non-discrimination policies: Director of the Office of Institutional Opportunity and Access, IOA@ku.edu, 1246 W. Campus Road, Room 153A, Lawrence, KS, 66045, (785)864-6414, 711 TTY.

     Contact KU
    Lawrence, KS | Maps