Neuronal protection by sirtuins in Alzheimer's disease

Thimmappa S. Anekonda, P. Hemachandra Reddy

    Research output: Contribution to journalReview article

    121 Scopus citations

    Abstract

    Silent information regulator 2, a member of NAD+-dependent histone deacetylase in yeast, and its homologs in mice and humans, participate in numerous important cell functions, including cell protection and cell cycle regulation. The sirtuin family members are highly conserved evolutionarily, and are predicted to have a role in cell survival. The science of sirtuins is an emerging field and is expected to contribute significantly to the role of sirtuins in healthy aging in humans. The role of sirtuins in neuronal protection has been studied in lower organisms, such as yeast, worms, flies and rodents. Both yeast Sir2 and mammalian sirtuin proteins are up-regulated under calorie-restricted and resveratrol treatments. Increased sirtuin expression protects cells from various insults. Caloric restriction and antioxidant treatments have shown useful effects in mouse models of aging and Alzheimer's disease (AD) and in limited human AD clinical trials. The role sirtuins may play in modifying and protecting neurons in patients with neurodegenerative diseases is still unknown. However, a recent report of Huntington's disease revealed that Sirtuin protects neurons in a Huntington's disease mouse model, suggesting that sirtuins may protect neurons in patients with neurodegenerative diseases, such as AD. In this review, we discuss the possible mechanisms of sirtuins involved in neuronal protection and the potential therapeutic value of sirtuins in healthy aging and AD.

    Original languageEnglish (US)
    Pages (from-to)305-313
    Number of pages9
    JournalJournal of neurochemistry
    Volume96
    Issue number2
    DOIs
    StatePublished - Jan 1 2006

    Keywords

    • Alzheimer's disease
    • Animal models
    • Calorie restriction
    • Healthy aging
    • Mitochondria
    • Sirtuins
    • Uncoupling proteins

    ASJC Scopus subject areas

    • Biochemistry
    • Cellular and Molecular Neuroscience

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