Mitochondrial dysfunction in aging and Alzheimer's disease: Strategies to protect neurons

P (Hemachandra) Reddy

    Research output: Contribution to journalArticle

    129 Citations (Scopus)

    Abstract

    Recent structural and functional studies of mitochondria have revealed that abnormalities in mitochondria may lead to mitochondrial dysfunction in aged individuals and those with neurodegenerative diseases, including Alzheimer's disease (AD). Molecular, cellular, and biochemical studies of animal models of aging and AD have provided compelling evidence that mitochondria are involved in AD development and progression. Further, a role for mitochondrial dysfunction in AD is supported by studies of neurons from autopsy specimens of patients with AD, transgenic AD mice, and neuronal cells expressing human AD mutation, which have revealed that amyloid beta (Aβ) enters mitochondria early in the disease process and disrupts the electron-transport chain, generates reactive oxygen species, and inhibits the production of cellular ATP, which in turn prevents neurons from functioning normally. Although AD researchers are actively involved in understanding Aβ toxicity and trying to develop strategies to reduce Aβ toxicity, one route they have yet to take is to investigate the molecules that activate nonamyloidogenic α-secretase activity that may reduce Aβ production and toxicity. In addition, it may be worthwhile to develop mitochondrially targeted antioxidants to treat AD. This article discusses critical issues of mitochondria causing dysfunction in aging and AD and discusses the strategies to protect neurons caused by mitochondrial dysfunction.

    Original languageEnglish (US)
    Pages (from-to)1647-1658
    Number of pages12
    JournalAntioxidants and Redox Signaling
    Volume9
    Issue number10
    DOIs
    StatePublished - Oct 2007

    Fingerprint

    Neurons
    Alzheimer Disease
    Aging of materials
    Mitochondria
    Toxicity
    Neurodegenerative diseases
    Amyloid Precursor Protein Secretases
    Electron Transport
    Amyloid
    Neurodegenerative Diseases
    Disease Progression
    Autopsy
    Reactive Oxygen Species
    Animal Models
    Antioxidants
    Adenosine Triphosphate
    Animals
    Research Personnel
    Cells
    Mutation

    ASJC Scopus subject areas

    • Biochemistry

    Cite this

    Mitochondrial dysfunction in aging and Alzheimer's disease : Strategies to protect neurons. / Reddy, P (Hemachandra).

    In: Antioxidants and Redox Signaling, Vol. 9, No. 10, 10.2007, p. 1647-1658.

    Research output: Contribution to journalArticle

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