Endoplasmic reticulum stress and the unfolded protein response: emerging regulators in progression of traumatic brain injury

Traumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease is still unsatisfactory. Therefore, it is necessary to investigate the pathophysiological mechanisms of TBI in depth to improve the treatment options. I...

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Bibliographic Details
Published in:Cell death & disease 2024-02, Vol.15 (2), p.156-15, Article 156
Main Authors: Yang, Yayi, Lu, Dengfeng, Wang, Menghan, Liu, Guangjie, Feng, Yun, Ren, Yubo, Sun, Xiaoou, Chen, Zhouqing, Wang, Zhong
Format: Article
Language:English
Subjects:
631/378/340
692/699/375/1345
Activating transcription factor 6
Antibodies
Autophagy
Biochemistry
Biomedical and Life Sciences
Brain Injuries, Traumatic
Cell Biology
Cell Culture
Cell death
Central nervous system
eIF-2 Kinase - genetics
eIF-2 Kinase - metabolism
Endoplasmic reticulum
Endoplasmic Reticulum Stress
Humans
Immunology
Inflammation
Inositol
Kinases
Life Sciences
Oxidative stress
Protein folding
Proteins
Review
Review Article
Traumatic brain injury
Unfolded Protein Response
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Summary:Traumatic brain injury (TBI) is a common trauma with high mortality and disability rates worldwide. However, the current management of this disease is still unsatisfactory. Therefore, it is necessary to investigate the pathophysiological mechanisms of TBI in depth to improve the treatment options. In recent decades, abundant evidence has highlighted the significance of endoplasmic reticulum stress (ERS) in advancing central nervous system (CNS) disorders, including TBI. ERS following TBI leads to the accumulation of unfolded proteins, initiating the unfolded protein response (UPR). Protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6) are the three major pathways of UPR initiation that determine whether a cell survives or dies. This review focuses on the dual effects of ERS on TBI and discusses the underlying mechanisms. It is suggested that ERS may crosstalk with a series of molecular cascade responses, such as mitochondrial dysfunction, oxidative stress, neuroinflammation, autophagy, and cell death, and is thus involved in the progression of secondary injury after TBI. Hence, ERS is a promising candidate for the management of TBI.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-024-06515-x