Regulation of Hypoxic Signaling and Oxidative Stress via the MicroRNA-SIRT2 Axis and Its Relationship with
Taku Kaitsuka1, Masayuki Matsushita2, Nobuko Matsushita3
1School of Pharmacy at Fukuoka, International University of Health and Welfare, Fukuoka 831-8501, Japan.
Abstract:
The sirtuin family of nicotinamide adenine dinucleotide-dependent deacetylase and ADP-ribosyl transferases plays key roles in aging, metabolism, stress response, and aging-related diseases. SIRT2 is a unique sirtuin that is expressed in the cytosol and is abundant in neuronal cells. Various microRNAs were recently reported to regulate SIRT2 expression via its 3'-untranslated region (UTR), and single nucleotide polymorphisms in the miRNA-binding sites of SIRT2 3'-UTR were identified in patients with neurodegenerative diseases. The present review highlights recent studies into SIRT2-mediated regulation of the stress response, posttranscriptional regulation of SIRT2 by microRNAs, and the implications of the SIRT2-miRNA axis in aging-related diseases.
Insights
Sirtuin 2 (SIRT2) is crucial for cellular stress response and neuronal health. MicroRNAs regulate SIRT2, and genetic variations in this interaction are linked to neurodegenerative diseases.
Area of Science:
- Biochemistry
- Molecular Biology
- Neuroscience
Background:
- Sirtuins, including SIRT2, are key regulators of metabolism, aging, and stress response.
- SIRT2, a cytosolic sirtuin abundant in neurons, plays a vital role in cellular functions.
- MicroRNAs (miRNAs) are increasingly recognized for their role in posttranscriptional gene regulation.
Purpose of the Study:
- To review the role of SIRT2 in stress response.
- To highlight the posttranscriptional regulation of SIRT2 by miRNAs.
- To discuss the implications of the SIRT2-miRNA axis in aging-related diseases, particularly neurodegeneration.
Main Methods:
- Literature review of recent studies on SIRT2.
- Analysis of research on miRNA regulation of SIRT2 expression via its 3'-untranslated region (UTR).
- Examination of studies linking single nucleotide polymorphisms (SNPs) in SIRT2 3'-UTR miRNA-binding sites to neurodegenerative diseases.
Main Results:
- SIRT2 is involved in mediating cellular stress responses.
- miRNAs posttranscriptionally regulate SIRT2 expression through its 3'-UTR.
- SNPs in SIRT2 3'-UTR miRNA-binding sites are associated with an increased risk of neurodegenerative diseases.
Conclusions:
- The SIRT2-miRNA axis is a critical regulatory pathway.
- Dysregulation of this axis contributes to the pathogenesis of aging-related diseases.
- Targeting the SIRT2-miRNA interaction may offer therapeutic strategies for neurodegenerative disorders.
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