Summary
Traumatic brain injury (TBI), as a serious central nervous system disease, can result in severe neurological dysfunction or even disability and death of patients. The early and effective intervention of secondary brain injury can improve the prognosis of TBI. Endoplasmic reticulum (ER) stress is one of the main reasons to recover TBI. ER stress inhibition may be beneficial in treating TBI. Sestrin2 is a crucial regulator of ER stress, and its activation can significantly improve TBI. In this paper, we analyze the biological function of sestrin2, the latest findings on ER stress, and the relationship between ER stress and TBI. We elucidate the relationship of sestrin2 inhibiting ER stress via activating the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin complex 1 (MTORC1) signaling. Finally, we elaborate on the possible role of sestrin2 in TBI and explain how its activation potentially improves TBI.
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Abbreviations
- TBI:
-
Traumatic brain injury
- ER:
-
Endoplasmic reticulum
- AMPK:
-
AMP-activated protein kinase
- mTORC1:
-
Mammalian target of rapamycin complex 1
- TSC:
-
Tuberous sclerosis complex
- PA26:
-
p53-activated gene 26
- ATF4:
-
Activating transcription factor 4
- Nrf2:
-
Nuclear factor erythroid-2-related factor 2
- WDR:
-
WD repeat domain 24
- GATOR1:
-
GTPase-activating protein activity toward Rags1
- RNF167:
-
RING finger protein 167
- STAMBPL1:
-
STAM-binding-protein-like 1
- UPR:
-
Unfolded protein response
- CHOP:
-
C/EBP homologous protein
- IRE1:
-
Inositol required kinase 1
- PERK:
-
Protein kinase R-like endoplasmic reticulum kinase
- mTOR:
-
Mechanistic target of rapamycin
- ULK1:
-
Unc-51 like autophagy activating kinase 1
- I/R:
-
Ischemia-reperfusion
- NF-κB:
-
Nuclear factor kappa B
- ROS:
-
Reactive oxygen species
- TON:
-
Traumatic optic neuropathy
- PDIA3:
-
Protein disulfide isomerase A3
- DNAJC3:
-
DNA J homology subfamily C member 3
- TBK1:
-
TANK-binding kinase 1
- PD:
-
Parkinson’s disease
- AD:
-
Alzheimer’s disease
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XL designed the study. YZ, YZ, BO.A.B, MH and XL prepared the first draft of the manuscript. YZ, BO.A.B, YZ, MH and XL revised the manuscript. All authors approved the final paper.
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Zhou, Y., Zhang, Y., Botchway, B.O. et al. Sestrin2 can alleviate endoplasmic reticulum stress to improve traumatic brain injury by activating AMPK/mTORC1 signaling pathway. Metab Brain Dis 39, 439–452 (2024). https://doi.org/10.1007/s11011-023-01323-2
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DOI: https://doi.org/10.1007/s11011-023-01323-2