Micro RNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β novel targets in sporadic Alzheimer's disease

Hirosha Geekiyanage, Christina Chan

    Research output: Research - peer-reviewArticle

    • 111 Citations

    Abstract

    The contribution of mutations in amyloid precursor protein (APP) and presenilin (PSEN) to familial Alzheimer's disease (AD) is well established. However, little is known about the molecular mechanisms leading to amyloidβ (Aβ) generation in sporadic AD. Increased brain ceramide levels have been associated with sporadic AD, and are a suggested risk factor. Serine palmitoyltransferase (SPT) is the first rate-limiting enzyme in the de novo ceramide synthesis. However, the regulation of SPT is not yet understood. Evidence suggests that it may be posttranscriptionally regulated. Therefore, we investigated the role of miRNAs in the regulation of SPT and amyloid β (Aβ) generation. We show that SPT is upregulated in a subgroup of sporadic AD patient brains. This is further confirmed in mouse model studies of risk factors associated with AD. We identified that the loss of miR-137, -181c, -9, and 29a/b-1 increases SPT and in turn Aβ levels, and provides a mechanism for the elevated risk of ADassociated with age, high-saturated-fat diet, and gender. Finally, these results suggest SPT and the respective miRNAs may be potential therapeutic targets for sporadic AD.

    LanguageEnglish (US)
    Pages14820-14830
    Number of pages11
    JournalJournal of Neuroscience
    Volume31
    Issue number41
    DOIs
    StatePublished - Oct 12 2011

    Profile

    Serine C-Palmitoyltransferase
    MicroRNAs
    Amyloid
    Alzheimer Disease
    Ceramides
    Brain
    Presenilins
    Amyloid beta-Protein Precursor
    High Fat Diet
    Mutation
    Enzymes
    Therapeutics

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Medicine(all)

    Cite this

    Micro RNA-137/181c regulates serine palmitoyltransferase and in turn amyloid β novel targets in sporadic Alzheimer's disease. / Geekiyanage, Hirosha; Chan, Christina.

    In: Journal of Neuroscience, Vol. 31, No. 41, 12.10.2011, p. 14820-14830.

    Research output: Research - peer-reviewArticle

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