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Integration of the deacetylase SIRT1 in the response to nucleolar stress:metabolic implications for neurodegenerative diseases

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peer-reviewed

Erstveröffentlichung
2019-04-26
Authors
Kreiner, Grzegorz
Sönmez, Aynur
Liß, Birgit
Parlato, Rosanna
Wissenschaftlicher Artikel


Published in
Frontiers in Molecular Neuroscience ; 12 (2019). - Art.-Nr. 106. - eISSN 1662-5099
Link to original publication
https://dx.doi.org/10.3389/fnmol.2019.00106
Faculties
Medizinische Fakultät
Institutions
Institut für Allgemeine Physiologie
External cooperations
Polish Academy of Sciences
University of Oxford
Universität Heidelberg
Document version
published version (publisher's PDF)
Abstract
Understanding underlying mechanisms of neurodegenerative diseases is fundamental to develop effective therapeutic intervention. Yet they remain largely elusive, but metabolic, and transcriptional dysregulation are common events. Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NADC)-dependent lysine deacetylase, regulating transcription, and critical for the cellular adaptations to metabolic stress. SIRT1 regulates the transcription of ribosomal RNA (rRNA), connecting the energetic state with cell growth and function. The activity of the transcription initiation factor-IA (TIF-IA) is important for the transcriptional regulation of ribosomal DNA (rDNA) genes in the nucleolus, and is also sensitive to changes in the cellular energetic state. Moreover, TIF-IA is responsive to nutrient-deprivation, neurotrophic stimulation, and oxidative stress. Hence, both SIRT1 and TIF-IA connect changes in cellular stress with transcriptional regulation and metabolic adaptation. Moreover, they finely tune the activity of the transcription factor p53, maintain mitochondrial function, and oxidative stress responses. Here we reviewed and discussed evidence that SIRT1 and TIF-IA are regulated by shared pathways and their activities preserve neuronal homeostasis in response to metabolic stressors. We provide evidence that loss of rDNA transcription due to altered TIF-IA function alters SIRT1 expression and propose a model of interdependent feedback mechanisms. An imbalance of this signaling might be a critical common event in neurodegenerative diseases. In conclusion, we provide a novel perspective for the prediction of the therapeutic benefits of the modulation of SIRT1- and nucleolar-dependent pathways in metabolic and neurodegenerative diseases.
DFG Project THU
GRK 1789 / CEMMA / Zelluläre und molekulare Mechanismen der Alterung / DFG / 194266605
Publication funding
Open-Access-Förderung durch die Medizinische Fakultät der Universität Ulm
Subject headings
[GND]: Nervendegeneration | Sirtuine | Oxidativer Stress | Ribosomale RNS | Protein p53
[LCSH]: Nervous system; Degeneration
[MeSH]: Neurodegenerative diseases | Sirtuins | Oxidative stress | RNA, Ribosomal
[Free subject headings]: nucleolus | rRNA | neuronal homeostasis | neurodegeneration
[DDC subject group]: DDC 610 / Medicine & health
License
CC BY 4.0 International
http://creativecommons.org/licenses/by/4.0/

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DOI & citation

Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-39182

Kreiner, Grzegorz et al. (2021): Integration of the deacetylase SIRT1 in the response to nucleolar stress:metabolic implications for neurodegenerative diseases. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-39182
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