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Sirtuins as Novel Biological Targets for Pharmacological Intervention in Physiology...
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Sirtuins as Novel Biological Targets for Pharmacological Intervention in Physiology and Pathology

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 January 2025 | Viewed by 2081

Special Issue Editors

Dr. Michele Aventaggiato

E-Mail Website
Guest Editor
Department of Experimental Medicine, Sapienza University of Rome, viale Regina Elena 324, 00161 Rome, Italy
Interests: sirtuins; metabolism; extracellular vesicles; autophagy; mitophagy; apoptosis
Dr. Marco Tafani

E-Mail Website
Guest Editor
Department of Experimental Medicine, Sapienza University, 00161 Rome, ItalyDepartment of Experimental Medicine, Sapienza University, Rome, Italy
Interests: sirtuins; hypoxia inflammation; metabolism; autophagy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The sirtuin family of proteins is a class of enzymes highly conserved from yeast to humans with a high homology in sequences and in their cellular functions, underlying the fact that these proteins play important physiological roles. Seven mammalian sirtuins have been identified, which are characterized by different cellular functions, structures and localizations that can vary following different stimuli. Sirtuins were first characterized as histone deacetylases, but the presence of non-histone targets underline their involvement in many cellular processes such as the cell cycle, differentiation, senescence, stress response, inflammation, aging and metabolism. On the other hand, sirtuins are involved in several pathological conditions, such as neurodegenerative disorders, cardiovascular diseases, metabolism-related disorders, carcinogenesis and tumor development, in which they can act as disease promoters or protective factors based on their targets and functions. Nuclear sirtuins, due to their epigenetic role, and mitochondrial sirtuins, due to their involvement in several metabolic processes such as the tricarboxylic acid cycle, respiratory chain, fatty acid β-oxidation, ketogenesis, glutamine metabolism, etc., represent an important object of investigation since one of the hallmarks of carcinogenesis is represented by metabolic reprogramming and uncontrolled cell proliferation. In a broader analysis that also considers the influence of sirtuins in physiological and pathological conditions, this class of proteins represents a promising potential target of molecular and pharmacological strategies that could counteract the effects of several pathological conditions acting at various levels in molecular and cellular mechanisms. This Special Issue aims to collect and summarize the latest findings on the potential pharmacological intervention to modulate sirtuins' activity in counteracting damage and the onset of pathological states and favors the physiological homeostasis of tissues.

Dr. Michele Aventaggiato
Dr. Marco Tafani
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • sirtuins
  • metabolism
  • cancer
  • hypoxia
  • damage recovery
  • cell death

Published Papers (2 papers)

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Research

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24 pages, 7124 KiB  
Article
Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH
by Michele Aventaggiato, Tania Arcangeli, Enza Vernucci, Federica Barreca, Luigi Sansone, Laura Pellegrini, Elena Pontemezzo, Sergio Valente, Rossella Fioravanti, Matteo Antonio Russo, Antonello Mai and Marco Tafani
Pharmaceuticals 2024, 17(6), 810; https://doi.org/10.3390/ph17060810 - 20 Jun 2024
Viewed by 641
Abstract
Cancer cells modulate their metabolism, creating an acidic microenvironment that, in turn, can favor tumor progression and chemotherapy resistance. Tumor cells adopt strategies to survive a drop in extracellular pH (pHe). In the present manuscript, we investigated the contribution of mitochondrial sirtuin 3 [...] Read more.
Cancer cells modulate their metabolism, creating an acidic microenvironment that, in turn, can favor tumor progression and chemotherapy resistance. Tumor cells adopt strategies to survive a drop in extracellular pH (pHe). In the present manuscript, we investigated the contribution of mitochondrial sirtuin 3 (SIRT3) to the adaptation and survival of cancer cells to a low pHe. SIRT3-overexpressing and silenced breast cancer cells MDA-MB-231 and human embryonic kidney HEK293 cells were grown in buffered and unbuffered media at pH 7.4 and 6.8 for different times. mRNA expression of SIRT3 and CAVB, was measured by RT-PCR. Protein expression of SIRT3, CAVB and autophagy proteins was estimated by western blot. SIRT3-CAVB interaction was determined by immunoprecipitation and proximity ligation assays (PLA). Induction of autophagy was studied by western blot and TEM. SIRT3 overexpression increases the survival of both cell lines. Moreover, we demonstrated that SIRT3 controls intracellular pH (pHi) through the regulation of mitochondrial carbonic anhydrase VB (CAVB). Interestingly, we obtained similar results by using MC2791, a new SIRT3 activator. Our results point to the possibility of modulating SIRT3 to decrease the response and resistance of tumor cells to the acidic microenvironment and ameliorate the effectiveness of anticancer therapy. Full article
(This article belongs to the Special Issue Sirtuins as Novel Biological Targets for Pharmacological Intervention in Physiology and Pathology)
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Review

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25 pages, 1810 KiB  
Review
Roles of Sirtuins in Hearing Protection
by Chail Koo, Claus-Peter Richter and Xiaodong Tan
Pharmaceuticals 2024, 17(8), 998; https://doi.org/10.3390/ph17080998 (registering DOI) - 28 Jul 2024
Viewed by 359
Abstract
Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate is the only drug approved by the Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in the search for new [...] Read more.
Hearing loss is a health crisis that affects more than 60 million Americans. Currently, sodium thiosulfate is the only drug approved by the Food and Drug Administration (FDA) to counter hearing loss. Sirtuins were proposed as therapeutic targets in the search for new compounds or drugs to prevent or cure age-, noise-, or drug-induced hearing loss. Sirtuins are proteins involved in metabolic regulation with the potential to ameliorate sensorineural hearing loss. The mammalian sirtuin family includes seven members, SIRT1-7. This paper is a literature review on the sirtuins and their protective roles in sensorineural hearing loss. Literature search on the NCBI PubMed database and NUsearch included the keywords ‘sirtuin’ and ‘hearing’. Studies on sirtuins without relevance to hearing and studies on hearing without relevance to sirtuins were excluded. Only primary research articles with data on sirtuin expression and physiologic auditory tests were considered. The literature review identified 183 records on sirtuins and hearing. After removing duplicates, eighty-one records remained. After screening for eligibility criteria, there were forty-eight primary research articles with statistically significant data relevant to sirtuins and hearing. Overall, SIRT1 (n = 29) was the most studied sirtuin paralog. Over the last two decades, research on sirtuins and hearing has largely focused on age-, noise-, and drug-induced hearing loss. Past and current studies highlight the role of sirtuins as a mediator of redox homeostasis. However, more studies need to be conducted on the involvement of SIRT2 and SIRT4-7 in hearing protection. Full article
(This article belongs to the Special Issue Sirtuins as Novel Biological Targets for Pharmacological Intervention in Physiology and Pathology)
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