SIRT3 Activation a Promise in Drug Development? New Insights into SIRT3 Biology and Its Implications on the Drug Discovery Process

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(3), С. 1662 - 1689

Опубликована: Янв. 23, 2024

Sirtuins catalyze deacetylation of lysine residues with a NAD

Язык: Английский

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Context-dependent role of SIRT3 in cancer

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 45(2), С. 173 - 190

Опубликована: Янв. 19, 2024

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Current Trends in Sirtuin Activator and Inhibitor Development

Molecules, Год журнала: 2024, Номер 29(5), С. 1185 - 1185

Опубликована: Март 6, 2024

Sirtuins are NAD+-dependent protein deacylases and key metabolic regulators, coupling the cellular energy state with selective lysine deacylation to regulate many downstream processes. Humans encode seven sirtuin isoforms (Sirt1-7) diverse subcellular localization deacylase targets. considered protective anti-aging proteins since increased activity is canonically associated lifespan extension decreased developing aging-related diseases. However, sirtuins can also assume detrimental roles where contributes pathophysiology. Modulation of by activators inhibitors thus holds substantial potential for defining in health disease therapeutics. Instead being comprehensive, this review discusses well-characterized available date, particularly those demonstrated selectivity, potency, activity. This provides recommendations regarding best-in-class practical research as modulator discovery refinement evolve.

Язык: Английский

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Mitochondrial Sirtuins in Cancer: A Revisited Review from Molecular Mechanisms to Therapeutic Strategies

Theranostics, Год журнала: 2024, Номер 14(7), С. 2993 - 3013

Опубликована: Янв. 1, 2024

The sirtuin (SIRT) family is well-known as a group of deacetylase enzymes that rely on nicotinamide adenine dinucleotide (NAD

Язык: Английский

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The role of neurovascular coupling dysfunction in cognitive decline of diabetes patients

Frontiers in Neuroscience, Год журнала: 2024, Номер 18

Опубликована: Март 21, 2024

Neurovascular coupling (NVC) is an important mechanism to ensure adequate blood supply active neurons in the brain. NVC damage can lead chronic impairment of neuronal function. Diabetes characterized by high sugar and considered risk factor for cognitive impairment. In this review, we provide fMRI evidence diabetic patients with decline. Combined exploration major mechanisms signaling pathways NVC, discuss effects hyperglycemia on cellular structure signaling, including key receptors, ion channels, intercellular connections. Studying these diabetes-related changes cell will help us understand underlying causes behind diabetes-induced early decline, ultimately helping identify most effective drug targets treatment.

Язык: Английский

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Activation and inhibition of sirtuins: From bench to bedside

Medicinal Research Reviews, Год журнала: 2024, Номер unknown

Опубликована: Авг. 31, 2024

Abstract The sirtuin family comprises seven NAD + ‐dependent enzymes which catalyze protein lysine deacylation and mono ADP‐ribosylation. Sirtuins act as central regulators of genomic stability gene expression control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, aging. As a result, all sirtuins play critical roles in cellular homeostasis organism wellness, their dysregulation has been linked to metabolic, cardiovascular, neurological diseases. Furthermore, have shown dichotomous cancer, acting context‐dependent tumor suppressors or promoters. Given role different attracted increasing research interest aimed at developing both activators inhibitors. Indeed, modulation may therapeutic effects many age‐related diseases, diabetes, cardiovascular neurodegenerative disorders, cancer. Moreover, isoform selective modulators increase our knowledge biology aid develop better therapies. Through this review, we provide insights into pharmacology illustrate enzymatic activities biological functions. outline the most relevant terms modes action, structure–activity relationships, pharmacological effects, clinical applications.

Язык: Английский

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Current Landscape of Hypoxia in Thyroid Cancer Pathogenesis and Treatment

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104719 - 104719

Опубликована: Апрель 1, 2025

Язык: Английский

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Unraveling Small Molecule-Mediated Sirtuin 3 Activation at a Distinct Binding Site for Cardioprotective Therapies

ACS Central Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 13, 2025

Язык: Английский

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Recent Advances on Mutant p53: Unveiling Novel Oncogenic Roles, Degradation Pathways, and Therapeutic Interventions

Biomolecules, Год журнала: 2024, Номер 14(6), С. 649 - 649

Опубликована: Май 31, 2024

The p53 protein is the master regulator of cellular integrity, primarily due to its tumor-suppressing functions. Approximately half all human cancers carry mutations in TP53 gene, which not only abrogate tumor-suppressive functions but also confer mutant proteins with oncogenic potential. latter achieved through so-called gain-of-function (GOF) that promote cancer progression, metastasis, and therapy resistance by deregulating transcriptional networks, signaling pathways, metabolism, immune surveillance, compositions microenvironment. Despite recent progress understanding complexity mutp53 neoplastic development, exact mechanisms how contributes development they escape proteasomal lysosomal degradation remain partially understood. In this review, we address findings field specifically regarding, limited to, implications metabolic secretome cells, microenvironment, regulating scenarios aberrant degradation. By analyzing degradation, as well connection autophagy, propose new therapeutical approaches aim destabilize deactivate functions, thereby providing a fundamental basis for further investigation rational treatment TP53-mutated cancers.

Язык: Английский

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Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?

Life, Год журнала: 2023, Номер 14(1), С. 23 - 23

Опубликована: Дек. 22, 2023

Cardiovascular disease (CVD) is the leading cause of death worldwide. In addition to high mortality rate, people suffering from CVD often endure difficulties with physical activities and productivity that significantly affect their quality life. The prevalence debilitating risk factors such as obesity, type 2 diabetes mellitus, smoking, hypertension, hyperlipidemia only predicts a bleak future. Current traditional interventions offer temporary respite; however, they compound severe economic strain health-related expenditures. Furthermore, these therapeutics can be prescribed indefinitely. Recent advances in field epigenetics have generated new treatment options by confronting at an epigenetic level. This involves modulating gene expression altering organization our genome rather than DNA sequence itself. Epigenetic changes are heritable, reversible, influenced environmental medications. As physiologically pathologically diverse nature, ray hope replace or combined provide prospect addressing more just symptoms CVD. review discusses various contributing CVD, perspectives current medications practice, focus on potential used alternatives.

Язык: Английский

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