Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease: Implications to mitochondria-targeted antioxidant therapeutics

P (Hemachandra) Reddy, Raghav Tripathi, Quang Troung, Karuna Tirumala, Tejaswini P. Reddy, Vishwanath Anekonda, Ulziibat P. Shirendeb, Marcus J. Calkins, Arubala Reddy, Peizhong Mao, Maria Manczak

    Research output: Contribution to journalArticle

    176 Citations (Scopus)

    Abstract

    Synaptic pathology and mitochondrial oxidative damage are early events in Alzheimer's disease (AD) progression. Loss of synapses and synaptic damage are the best correlates of cognitive deficits found in AD patients. Recent research on amyloid beta (Aβ) and mitochondria in AD revealed that Aβ accumulates in synapses and synaptic mitochondria, leading to abnormal mitochondrial dynamics and synaptic degeneration in AD neurons. Further, recent studies using live-cell imaging and primary neurons from amyloid beta precursor protein (AβPP) transgenic mice revealed reduced mitochondrial mass, defective axonal transport of mitochondria and synaptic degeneration, indicating that Aβ is responsible for mitochondrial and synaptic deficiencies. Tremendous progress has been made in studying antioxidant approaches in mouse models of AD and clinical trials of AD patients. This article highlights the recent developments made in Aβ-induced abnormal mitochondrial dynamics, defective mitochondrial biogenesis, impaired axonal transport and synaptic deficiencies in AD. This article also focuses on mitochondrial approaches in treating AD, and also discusses latest research on mitochondria-targeted antioxidants in AD. This article is part of a Special Issue entitled: Antioxidants and Antioxidant Treatment in Disease.

    Original languageEnglish (US)
    Pages (from-to)639-649
    Number of pages11
    JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
    Volume1822
    Issue number5
    DOIs
    StatePublished - May 2012

    Fingerprint

    Mitochondrial Dynamics
    Alzheimer Disease
    Mitochondria
    Antioxidants
    Axonal Transport
    Therapeutics
    Synapses
    Neurons
    Amyloid beta-Protein Precursor
    Organelle Biogenesis
    Research
    Amyloid
    Transgenic Mice
    Disease Progression
    Clinical Trials
    Pathology

    Keywords

    • Alzheimer's disease
    • Amyloid beta
    • Amyloid precursor protein
    • Antioxidant
    • Primary neuron
    • Reactive oxygen species

    ASJC Scopus subject areas

    • Molecular Biology
    • Molecular Medicine

    Cite this

    Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease : Implications to mitochondria-targeted antioxidant therapeutics. / Reddy, P (Hemachandra); Tripathi, Raghav; Troung, Quang; Tirumala, Karuna; Reddy, Tejaswini P.; Anekonda, Vishwanath; Shirendeb, Ulziibat P.; Calkins, Marcus J.; Reddy, Arubala; Mao, Peizhong; Manczak, Maria.

    In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1822, No. 5, 05.2012, p. 639-649.

    Research output: Contribution to journalArticle

    Reddy, P (Hemachandra) ; Tripathi, Raghav ; Troung, Quang ; Tirumala, Karuna ; Reddy, Tejaswini P. ; Anekonda, Vishwanath ; Shirendeb, Ulziibat P. ; Calkins, Marcus J. ; Reddy, Arubala ; Mao, Peizhong ; Manczak, Maria. / Abnormal mitochondrial dynamics and synaptic degeneration as early events in Alzheimer's disease : Implications to mitochondria-targeted antioxidant therapeutics. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2012 ; Vol. 1822, No. 5. pp. 639-649.
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