Amyloid precursor protein-mediated free radicals and oxidative damage: Implications for the development and progression of Alzheimer's disease

P. Hemachandra Reddy

    Research output: Contribution to journalReview article

    274 Scopus citations

    Abstract

    Alzheimer's disease (AD) is a late-onset dementia that is characterized by the loss of memory and an impairment of multiple cognitive functions. Advancements in molecular, cellular, and animal model studies have revealed that the formation of amyloid beta (Aβ) and other derivatives of the amyloid precursor protein (APP) are key factors in cellular changes in the AD brain, including the generation of free radicals, oxidative damage, and inflammation. Recent molecular, cellular, and gene expression studies have revealed that Aβ enters mitochondria, induces the generation of free radicals, and leads to oxidative damage in post-mortem brain neurons from AD patients and in brain neurons from cell models and transgenic mouse models of AD. In the last three decades, tremendous progress has been made in mitochondrial research and has provided significant findings to link mitochondrial oxidative damage and neurodegenerative diseases such as AD. Researchers in the AD field are beginning to recognize the possible involvement of a mutant APP and its derivatives in causing mitochondrial oxidative damage in AD. This article summarizes the latest research findings on the generation of free radicals in mitochondria and provides a possible model that links Aβ proteins, the generation of free radicals, and oxidative damage in AD development and progression.

    Original languageEnglish (US)
    Pages (from-to)1-13
    Number of pages13
    JournalJournal of Neurochemistry
    Volume96
    Issue number1
    DOIs
    StatePublished - Jan 1 2006

    Keywords

    • In vitro studies
    • Mitochondria
    • Mitochondrial gene expression
    • Oxidative damage
    • Reactive oxygen species
    • Transgenic mice

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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