Emerging roles of sestrins in neurodegenerative diseases: Counteracting oxidative stress and beyond

Shang Der Chen, Jenq Lin Yang, Tsu Kung Lin, Ding I. Yang*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Scopus citations


Low levels of reactive oxygen species (ROS) are critical for the operation of regular neuronal function. However, heightened oxidative stress with increased contents of oxidation markers in DNA, lipids, and proteins with compromised antioxidant capacity may play a harmful role in the brain and may be implicated in the pathophysiology of neurodegenerative diseases. Sestrins, a family of evolutionarily-conserved stress-inducible proteins, are actively regulated by assorted stresses, such as DNA damage, hypoxia, and oxidative stress. Three highly homologous genes that encode sestrin1, sestrin2, and sestrin3 proteins exist in the genomes of vertebrates. Under stressful conditions, sestrins are activated with versatile functions to cope with different types of stimuli. A growing body of evidence suggests that sestrins, especially sestrin2, can counteract oxidative stress, lessen mammalian/mechanistic target of rapamycin (mTOR) expression, and promote cell survival, thereby playing a critical role in aging-related disorders including neurodegeneration. Strategies capable of augmenting sestrin expression may; thus, facilitate cell adaptation to stressful conditions or environments through stimulation of antioxidant response and autophagy process, which may carry clinical significance in neurodegenerative diseases.

Original languageEnglish
Article number1001
JournalJournal of Clinical Medicine
Issue number7
StatePublished - Jul 2019


  • Autophagy
  • MTOR
  • Neurodegenerative diseases
  • Oxidative stress
  • Sestrins


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