Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Jęśko, Henryk; Strosznajder, Robert P.

doi:10.5114/fn.2016.62531

Cited by 34 publications

(26 citation statements)

References 235 publications

(275 reference statements)

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“…During the past decade, there has been significant progress in understanding the role of sirtuins in brain aging and in neurodegenerative disorders such as AD [1, 16]. Till now relatively little is known about the role of SIRTs in PD or Huntighton’s disease [5, 196].…”

Section: Resultsmentioning

confidence: 99%

“…Weakened trophic support of neurons and the resulting nuclear accumulation of FOXO3a transcription factor might be an important aspect [194]. The role of sirtuins in neuronal survival and the known interactions with huntingtin [195] and FOXOs [1] made them a plausible research target. However, sirtuins’ role in HD is somewhat controversial, likely stemming from their wide, pleiotropic spectrum of signaling interactions [193].…”

Section: Sirtuins In Neurodegeneration and Neuroprotectionmentioning

confidence: 99%

“…These enzymes modulate the properties and functions of proteins (e.g. histones, kinases, and transcription factors-TFs) [1, 2] by removing acetyl groups post-translationally attached to their lysine residues by acetyltransferases. Sirtuins are class III HDACs and differ from other classes in that they require NAD + for their activity.…”

Section: Introductionmentioning

confidence: 99%

“…Some sirtuins also possess additional enzymatic activities such as mono(ADP-ribosyl)ation (SIRT3, SIRT4, SIRT6), the ability to remove a wide array of other lysine modifications (e.g. desuccinylation and demalonylation—SIRT5; decrotonylation—SIRT1–3), and/or lack detectable deacetylation capability (SIRT4) [1, 2]. Sirtuins are engaged in cross-talk with a wide spectrum of transcription factors, including forkhead box subgroup O (FOXOs), p53, and NF-κB, and with proteins engaged in DNA repair such as DNA-dependent protein kinase (DNA-PK) [1, 4].…”

Section: Introductionmentioning

confidence: 99%

“…desuccinylation and demalonylation—SIRT5; decrotonylation—SIRT1–3), and/or lack detectable deacetylation capability (SIRT4) [1, 2]. Sirtuins are engaged in cross-talk with a wide spectrum of transcription factors, including forkhead box subgroup O (FOXOs), p53, and NF-κB, and with proteins engaged in DNA repair such as DNA-dependent protein kinase (DNA-PK) [1, 4]. The versatile and ubiquitous family of poly(ADP-ribose) polymerases (PARPs) shares the feature of NAD + -dependence with sirtuins; the two classes of enzymes compete for the substrate and interact in numerous ways, influencing a very broad range of cellular functions [1, 4].…”

Section: Introductionmentioning

confidence: 99%

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Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

et al. 2016

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Sirtuins (SIRT1–SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD+ levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD+-dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer’s disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Sirtuins In Neurodegeneration and Neuroprotectionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

et al. 2016

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Versatile role of sirtuins in metabolic disorders: From modulation of mitochondrial function to therapeutic interventions

Afzaal

Rehman

Kamal

et al. 2022

J Biochem & Molecular Tox

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The insights into molecular pathways of hypoxia‐inducible factor in the brain

Ostrowski

Zhang

2018

J of Neuroscience Research

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The objectives of this present work were to review recent developments on the role of hypoxia‐inducible factor (HIF) in the survival of cells under normoxic versus hypoxic and inflammatory brain conditions. The dual nature of HIF effects appears well established, based on the accumulated evidence of HIF playing both the role of adaptive factor and mediator of cell demise. Cellular HIF responses depend on pathophysiological conditions, developmental phase, comorbidities, and administered medications. In addition, HIF‐1α and HIF‐2α actions may vary in the same tissues. The multiple roles of HIF in stem cells are emerging. HIF not only regulates expression of target genes and thereby influences resultant protein levels but also contributes to epigenetic changes that may reciprocally provide feedback regulations loops. These HIF‐dependent alterations in neurological diseases and its responses to treatments in vivo need to be examined alongside with a functional status of subjects involved in such studies. The knowledge of HIF pathways might be helpful in devising HIF‐mimetics and modulating drugs, acting on the molecular level to improve clinical outcomes, as exemplified here by clinical and experimental data of selected brain diseases, occasionally corroborated by the data from disorders of other organs. Because of complex role of HIF in brain injuries, prospective therapeutic interventions need to differentially target HIF responses depending on their roles in the molecular mechanisms of neurologic diseases.

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Sirtuins and their interactions with transcription factors and poly(ADP-ribose) polymerases

Cited by 34 publications

References 235 publications

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders

Versatile role of sirtuins in metabolic disorders: From modulation of mitochondrial function to therapeutic interventions

The insights into molecular pathways of hypoxia‐inducible factor in the brain

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