Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

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Linan Gong1, Zanzan Wang1, Zhenggui Wang1

  • 1Center for Cardiovascular Medicine, First Hospital of Jilin University, Changchun, China.

Frontiers in Endocrinology
|November 22, 2021
PubMed

Insights

Sestrin2 protein, induced by cellular stress, regulates metabolism by influencing the AMPK/mTOR pathway. Modulating Sestrin2 offers a potential therapeutic strategy for metabolic diseases.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cellular Stress Response
  • Metabolic Regulation

Background:

  • Sestrin2 is a conserved protein upregulated by various cellular stresses like DNA damage, oxidative, ER, and metabolic stress.
  • The AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signaling pathways are critical regulators of cellular metabolism.
  • Dysregulation of these pathways is implicated in numerous metabolic disorders.

Purpose of the Study:

  • To review the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway.
  • To elucidate the effects of Sestrin2 on cellular energy metabolism.
  • To explore the therapeutic potential of Sestrin2 modulation for metabolic diseases.

Main Methods:

  • Literature review of studies investigating Sestrin2 function.
  • Analysis of Sestrin2's role in cellular stress response pathways.
  • Examination of Sestrin2's impact on AMPK/mTOR signaling and metabolic processes.

Main Results:

  • Sestrin2 modulates metabolism through AMPK activation, mTORC1 inhibition, mTORC2 activation, ER stress reduction, and autophagy promotion.
  • Sestrin2 plays a key role in maintaining metabolic homeostasis under stress conditions.
  • Evidence suggests Sestrin2 influences insulin resistance, diabetes, obesity, and liver/heart conditions.

Conclusions:

  • Sestrin2 is a critical mediator linking cellular stress to metabolic adaptation via the AMPK/mTOR pathway.
  • Targeting Sestrin2 presents a promising therapeutic avenue for preventing and treating a spectrum of metabolic diseases.
  • Further research into Sestrin2's precise mechanisms could unlock novel treatment strategies.
Keywords:
AMPKSestrin2mTORmetabolic diseasesmetabolism

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