Evidence for nucleolar dysfunction in Alzheimer's disease

Caitlin Nyhus, Maria Pihl, Poul Hyttel, Vanessa Jane Hall

    Abstract

    The nucleolus is a dynamically changing organelle that is central to a number of important cellular functions. Not only is it important for ribosome biogenesis, but it also reacts to stress by instigating a nucleolar stress response and is further involved in regulating the cell cycle. Several studies report nucleolar dysfunction in Alzheimer’s disease (AD). Studies have reported a decrease in both total nucleolar volume and transcriptional activity of the nucleolar organizing regions. Ribosomes appear to be targeted by oxidation and reduced protein translation has been reported. In addition, several nucleolar proteins are dysregulated and some of these appear to be implicated in classical AD pathology. Some studies also suggest that the nucleolar stress response may be activated in AD, albeit this latter research is rather limited and requires further investigation. The purpose of this review is to draw the connections of all these studies together and signify that there are clear changes in the nucleolus and the ribosomes in AD. The nucleolus is therefore an organelle that requires more attention than previously given in relation to understanding the biological mechanisms underlying the disease.
    OriginalsprogEngelsk
    TidsskriftReviews in the Neurosciences
    Vol/bind30
    Udgave nummer7
    Sider (fra-til)685–700
    ISSN0334-1763
    DOI
    StatusUdgivet - 2019

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