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Licensed Unlicensed Requires Authentication Published by De Gruyter March 8, 2019

Evidence for nucleolar dysfunction in Alzheimer’s disease

  • Caitlin Nyhus , Maria Pihl , Poul Hyttel and Vanessa Jane Hall EMAIL logo

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.

Acknowledgments

Financial support for costs related to the production and publication of this manuscript was from the Danish Council for Independent Research (Denmark) and the Innovation Fund Denmark (BrainStem).

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Received: 2018-10-19
Accepted: 2019-01-08
Published Online: 2019-03-08
Published in Print: 2019-10-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

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