Emerging Roles of Sestrins in Neurodegenerative Diseases: Counteracting Oxidative Stress and Beyond

Chen, Shang-Der; Yang, Jenq-Lin; Lin, Tay-Jyi; Yang, Ding

doi:10.3390/jcm8071001

Cited by 46 publications

(34 citation statements)

References 106 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ubiquitin-binding protein p62 enhances Keap-1-Nrf2 dissociation and facilitates degradation of Keap1 by p62-dependent autophagy, further stimulating the antioxidant response [ 88 , 89 ]. In addition, sestrins (SESNs), proteins involved in protecting cells from oxidative stress also promote p62-dependent autophagic degradation of Keap-1 [ 90 ]. Therefore, there is a close relationship between oxidative stress and autophagy where oxidative stress can induce autophagy through various mechanisms and vice-versa [ 36 , 91 ].…”

Section: The Relationship Between Reactive Oxygen Species and Autophamentioning

confidence: 99%

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

et al. 2020

View full text Add to dashboard Cite

The autophagic pathway involves the encapsulation of substrates in double-membraned vesicles, which are subsequently delivered to the lysosome for enzymatic degradation and recycling of metabolic precursors. Autophagy is a major cellular defense against oxidative stress, or related conditions that cause accumulation of damaged proteins or organelles. Selective forms of autophagy can maintain organelle populations or remove aggregated proteins. Dysregulation of redox homeostasis under pathological conditions results in excessive generation of reactive oxygen species (ROS), leading to oxidative stress and the associated oxidative damage of cellular components. Accumulating evidence indicates that autophagy is necessary to maintain redox homeostasis. ROS activates autophagy, which facilitates cellular adaptation and diminishes oxidative damage by degrading and recycling intracellular damaged macromolecules and dysfunctional organelles. The cellular responses triggered by oxidative stress include the altered regulation of signaling pathways that culminate in the regulation of autophagy. Current research suggests a central role for autophagy as a mammalian oxidative stress response and its interrelationship to other stress defense systems. Altered autophagy phenotypes have been observed in lung diseases such as chronic obstructive lung disease, acute lung injury, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension, and asthma. Understanding the mechanisms by which ROS regulate autophagy will provide novel therapeutic targets for lung diseases. This review highlights our current understanding on the interplay between ROS and autophagy in the development of pulmonary disease.

show abstract

Section: The Relationship Between Reactive Oxygen Species and Autophamentioning

confidence: 99%

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Recent studies suggest that Sestrins improve longevity and elderly health by suppressing ROS, regulating autophagy activity and protecting metabolic dysfunction in muscle, heart and brain (Rai et al, 2018;Chen et al, 2019;Cordani et al, 2019;Fan et al, 2020;Liu et al, 2020;Segales et al, 2020;Sun et al, 2020). The level of Sestrins expression is downregulated in aged men although it has no clear correlation with autophagy activity, mTORC1 activity and antioxidant regulation (Zeng et al, 2018a).…”

Section: Sestrins In Environmental Stress and Agingmentioning

confidence: 99%

“…These studies indicate that maintaining the homeostatic level of Sesn2 is protective against cardiovascular aging (Liu et al, 2020;Sun et al, 2020). Sesn2 promoted autophagy in the brain and prevented neurodegenerative diseases by alleviating oxidative stress (Chen et al, 2019;Luo et al, 2020). Sesn2 protects neuronal cells from cerebral ischemia-reperfusion injury by increasing Nrf2, Srx1, and thioredoxin (Trx) 1 (Zhang and Zhang, 2018).…”

Section: Sestrins In Environmental Stress and Agingmentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

show abstract

“…Sestrin (Sesn) family members, including Sesn1, Sesn2, and Sesn3 in mammals, are proteins that regulate oxidative stress both in vivo and in vitro [6,7]. Sesn is widely present in a variety of tissues and organs, and its expression is majorly regulated by oxidative stress levels and, to a lesser extent, by inflammatory responses, aging, and other pathophysiological effects [8][9][10]. A number of studies have confirmed that Sesns are involved in the development and progression of various diseases, by regulating oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Circulating Sestrin Levels Are Increased in Hypertension Patients

et al. 2020

View full text Add to dashboard Cite

Background. Sestrins (Sesns), a group of oxidative stress-related proteins, have been reported to be involved in various cardiovascular diseases, including aortic dissection and chronic heart failure. This study is aimed at investigating the level of circulating Sesn1, Sesn2, and Sesn3 in hypertension patients. Methods. Plasma levels of Sesn1, Sesn2, and Sesn3 in 400 hypertensive patients and 100 normotensive subjects were detected using enzyme-linked immunosorbent assay (ELISA) kits. The hypertension patients were divided into groups with grade I (n=140), grade II (n=180), and grade III (n=80) hypertension. Results. Compared with the normotensive subjects, Sesn1, Sesn2, and Sesn3 levels were increased in patients with hypertension, with a gradual increase between the groups with grade I, grade II, and grade III hypertension. Elevated Sesn1, Sesn2, and Sesn3 levels were positively correlated with both the systolic blood pressure (SBP) and diastolic blood pressure (DBP). Moreover, Sesn1, Sesn2, and Sesn3 levels were elevated in patients with dipper hypertension and further increased in patients with nondipper hypertension. In addition, smokers, as well as patients with higher levels of angiotensin II (Ang II) and carotid atherosclerotic plaque (CAP), exhibited increased Sesn1, Sesn2, and Sesn3 levels when compared with patients without these clinical characteristics. Furthermore, plasma levels of Sesn1, Sesn2, and Sesn3 were negatively correlated with the presence of CAP. Conclusions. Circulating Sesn levels are increased in patients with hypertension and may be a target for the prevention and treatment of clinical hypertension.

show abstract

Emerging Roles of Sestrins in Neurodegenerative Diseases: Counteracting Oxidative Stress and Beyond

Cited by 46 publications

References 106 publications

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

Complex interplay between autophagy and oxidative stress in the development of pulmonary disease

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Circulating Sestrin Levels Are Increased in Hypertension Patients

Contact Info

Product

Resources

About