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Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?

Rosanna Parlato Holger Bierhoff

*Corresponding author: Rosanna Parlato rosanna.parlato@uni-ulm.de

Molecular2015,3,211doi:10.3934/molsci.2015.3.211

Within the cell nucleus the nucleolus is the site of rRNA transcription and ribosome biogenesis and its activity is clearly essential for a correct cell function, however its specific role in neuronal homeostasis remains mainly unknown. Here we review recent evidence that impaired nucleolar activity is a common mechanism in different neurodegenerative disorders. We focus on the specific causes and consequences of impaired nucleolar activity to better understand the pathogenesis of neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD). In particular, we discuss the genetic and epigenetic factors that might regulate nucleolar function in these diseases. In addition, we describe novel animal models enabling the dissection of the context-specific series of events triggered by nucleolar disruption, also known as nucleolar stress. Finally, we suggest how this novel mechanism could help to identify strategies to treat these still incurable disorders.

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