Sestrins at the Interface of ROS Control and Autophagy Regulation in Health and Disease.
Marco CordaniMiguel Sánchez-ÁlvarezRaffaele StrippoliAlexandr V BazhinMassimo DonadelliPublished in: Oxidative medicine and cellular longevity (2019)
Reactive oxygen species (ROS) and autophagy are two highly complex and interrelated components of cell physiopathology, but our understanding of their integration and their contribution to cell homeostasis and disease is still limited. Sestrins (SESNs) belong to a family of highly conserved stress-inducible proteins that orchestrate antioxidant and autophagy-regulating functions protecting cells from various noxious stimuli, including DNA damage, oxidative stress, hypoxia, and metabolic stress. They are also relevant modulators of metabolism as positive regulators of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibitors of mammalian target of rapamycin complex 1 (mTORC1). Since perturbations in these pathways are central to multiple disorders, SESNs might constitute potential novel therapeutic targets of broad interest. In this review, we discuss the current understanding of regulatory and effector networks of SESNs, highlighting their significance as potential biomarkers and therapeutic targets for different diseases, such as aging-related diseases, metabolic disorders, neurodegenerative diseases, and cancer.
Keyphrases
- oxidative stress
- dna damage
- cell death
- reactive oxygen species
- protein kinase
- endoplasmic reticulum stress
- single cell
- transcription factor
- signaling pathway
- induced apoptosis
- cell therapy
- diabetic rats
- dna repair
- ischemia reperfusion injury
- healthcare
- mental health
- public health
- small molecule
- stem cells
- papillary thyroid
- stress induced
- health information
- dendritic cells
- immune response
- risk assessment
- mesenchymal stem cells
- bone marrow
- drug induced
- childhood cancer
- squamous cell