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    Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore

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    YanShirley_Pharmace_3(6)1936.pdf (241.5Kb)
    Issue Date
    2010-05-10
    Author
    Du, Heng
    Yan, Shirley ShiDu
    Publisher
    MDPI
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    Mitochondrial dysfunction occurs early in the progression of Alzheimer’s disease. Amyloid-β peptide has deleterious effects on mitochondrial function and contributes to energy failure, respiratory chain impairment, neuronal apoptosis, and generation of reactive oxygen species in Alzheimer’s disease. The mechanisms underlying amyloid-β induced mitochondrial stress remain unclear. Emerging evidence indicates that mitochondrial permeability transition pore is important for maintenance of mitochondrial and neuronal function in aging and neurodegenerative disease. Cyclophilin D (Cyp D) plays a central role in opening mitochondrial permeability transition pores, ultimately leading to cell death. Interaction of amyloid-β with cyclophilin D triggers or enhances the formation of mitochondrial permeability transition pores, consequently exacerbating mitochondrial and neuronal dysfunction, as shown by decreased mitochondrial membrane potential, impaired mitochondrial respiration function, and increased oxidative stress and cytochrome c release. Blockade of cyclophilin D by genetic abrogation or pharmacologic inhibition protects mitochondria and neurons from amyloid-β induced toxicity, suggesting that cyclophilin D dependent mitochondrial transition pores are a therapeutic target for Alzheimer’s disease.
    Description
    This is the published version. Copyright 2010 MDPI.
    URI
    http://hdl.handle.net/1808/17871
    DOI
    https://doi.org/10.3390/ph3061936
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    • Pharmacy Scholarly Works [286]
    Citation
    Du, Heng, and Shirley Shidu Yan. "Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore." Pharmaceuticals 3.6 (2010): 1936-948. http://dx.doi.org/10.3390/ph3061936.

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    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
     

     

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