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J Mol Med (Berl). 2013 May;91(5):541-7. doi: 10.1007/s00109-012-0981-1. Epub 2012 Nov 20.

Nucleolar activity in neurodegenerative diseases: a missing piece of the puzzle?

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Department of Molecular Biology of the Cell I, DKFZ-ZMBH Alliance, German Cancer Research Center, Im Neuenheimer Feld, 581, 69120, Heidelberg, Germany.


Nucleoli are the sites where synthesis of rRNA and ribosomal assembly take place. Along with these "traditional" roles, the nucleolus controls cellular physiology and homeostasis. The cellular and molecular alterations associated with impaired nucleolar activity ("nucleolar stress") have just started to be systematically explored in the nervous system taking advantage of newly available animal models lacking rRNA synthesis in specific neurons. These studies showed that nucleolar function is necessary for neuronal survival and that its modality of action differs between and within cell types. Nucleolar function is also crucial in pathology as it controls mitochondrial activity and critical stress signaling pathways mimicking hallmarks of human neurodegenerative diseases. This mini-review will focus on the modes of action of nucleolar stress and discuss how the manipulation of nucleolar activity might underscore novel strategies to extend neuronal function and survival.

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