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

Rosanna Parlato; Holger Bierhoff; Rosanna Parlato; Holger Bierhoff

doi:10.3934/molsci.2015.3.211

AIMS Molecular Science

2015, Volume 2, Issue 3: 211-224. doi: 10.3934/molsci.2015.3.211

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

Rosanna Parlato ^{1,2
,
,},
Holger Bierhoff ³

1.
Institute of Applied Physiology, University of Ulm, Ulm, Germany;
2.
Institute of Anatomy and Cell Biology, Department of Medical Biology, University of Heidelberg, Heidelberg, Germany;
3.
Dept. of Molecular Biology of the Cell II, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany

Received: 15 April 2015 Accepted: 26 May 2015 Published: 29 May 2015

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.
- nucleolus,
- cellular stress,
- rRNA,
- neurodegeneration,
- mouse models,
- epigenetic regulation
Citation: Rosanna Parlato, Holger Bierhoff. Role of nucleolar dysfunction in neurodegenerative disorders: a game of genes?[J]. AIMS Molecular Science, 2015, 2(3): 211-224. doi: 10.3934/molsci.2015.3.211

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Abstract

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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