Sirtuins as endogenous regulators of lung fibrosis: A current perspective
| Autor: | Mukta Barman, Somnath Mazumder, Uday Bandyopadhyay, Samik Bindu |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
SIRT6 SIRT5 SIRT3 Pulmonary Fibrosis SIRT2 Bioinformatics 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Idiopathic pulmonary fibrosis 0302 clinical medicine Fibrosis Medicine Animals Humans Sirtuins Molecular Targeted Therapy General Pharmacology Toxicology and Pharmaceutics Lung biology business.industry General Medicine medicine.disease Mitochondria 030104 developmental biology medicine.anatomical_structure Sirtuin biology.protein business Signal Transduction |
| Zdroj: | Life sciences. 258 |
| ISSN: | 1879-0631 |
| Popis: | Fibrotic lung diseases qualify among the most dreaded irreversible interstitial pulmonary complications with progressive yet largely unpredictable clinical course. Idiopathic pulmonary fibrosis (IPF) is the most challenging prototype characterized by unknown and complex molecular etiology, severe dearth of non-invasive therapeutic options and average lifespan of 2–5 years in patients post diagnosis. Lung fibrosis (LF) is a leading cause of death in the industrialized world with the propensity to contract, significantly increasing with age. Approximately 45% deaths in US are attributed to fibrotic diseases while around 7% respiratory disease-associated deaths, annually in UK, are actually attributed to IPF. Recent developments in the field of LF have unambiguously pointed towards the pivotal role of Sirtuins (SIRTs) in regulating disease progression, thereby qualifying as potential anti-fibrotic drug targets. These NAD+-dependent lysine deacetylases, deacylases and ADP-ribosyltransferases are evolutionarily conserved proteins, regulated by diverse metabolic/environmental factors and implicated in age-related degenerative and inflammatory disorders. While SIRT1, SIRT6 and SIRT7 are predominantly nuclear, SIRT3, SIRT4, SIRT5 are mainly mitochondrial and SIRT2 is majorly cytosolic with occasional nuclear translocation. SIRT1, SIRT3, SIRT6 and SIRT7 are documented as cytoprotective sirtuins implicated in cardiovascular, pulmonary and metabolic diseases including fibrosis; however functional roles of remaining sirtuins in pulmonary pathologies are yet elusive. Here, we provide a comprehensive recent update on the regulatory role of sirtuins on LF along with discussion on potential therapeutic modulation of endogenous Sirtuin expression through synthetic/plant-derived compounds which can help synthetic chemists and ethnopharmacologists to design new-generation cheap, non-toxic Sirtuin-based drugs against LF. |
| Databáze: | OpenAIRE |
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