TY - JOUR
T1 - Sestrins at the Interface of ROS Control and Autophagy Regulation in Health and Disease
AU - Cordani, Marco
AU - Sánchez-Álvarez, Miguel
AU - Strippoli, Raffaele
AU - Bazhin, Alexandr V.
AU - Donadelli, Massimo
PY - 2019/5/7
Y1 - 2019/5/7
N2 - 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.
AB - 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.
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U2 - 10.1155/2019/1283075
DO - 10.1155/2019/1283075
M3 - Review article
C2 - 31205582
AN - SCOPUS:85068207878
VL - 2019
SP - 1
EP - 12
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
SN - 1942-0900
ER -