scholarly journals Integrated Stress Response as a Therapeutic Target for CNS Injuries

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Lorenzo Romero-Ramírez ◽  
Manuel Nieto-Sampedro ◽  
M. Asunción Barreda-Manso
Keyword(s):  
Central Nervous System ◽  
Stress Response ◽  
Small Molecules ◽  
Therapeutic Target ◽  
Protective Mechanism ◽  
Diverse Group ◽  
Integrated Stress Response ◽  
Cns Injury ◽  
Injury Repair

Central nervous system (CNS) injuries, caused by cerebrovascular pathologies or mechanical contusions (e.g., traumatic brain injury, TBI) comprise a diverse group of disorders that share the activation of the integrated stress response (ISR). This pathway is an innate protective mechanism, with encouraging potential as therapeutic target for CNS injury repair. In this review, we will focus on the progress in understanding the role of the ISR and we will discuss the effects of various small molecules that target the ISR on different animal models of CNS injury.

scholarly journals Emerging Role of the Integrated Stress Response upon Viral Infection

2020 ◽  
Author(s):  
Yongshu Wu ◽  
Xiaodong Qin ◽  
Meera Prajapati ◽  
Yijing Li ◽  
Zhidong Zhang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Amino Acid ◽  
Stress Response ◽  
Viral Infection ◽  
Cellular Stress Response ◽  
Protective Mechanism ◽  
Misfolded Protein ◽  
Integrated Stress Response ◽  
Amino Acid Deprivation

The integrated stress response (ISR) is an adaptational signaling pathway that is induced in response to different stimuli, such as accumulation of unfolded and misfolded protein, hypoxia, amino acid deprivation, viral infection and ultraviolet light. It has been known that viral infection can activate ISR, but the role of ISR during viral infection is still unclear. In some cases, ISR is a protective mechanism of host cell against infection with virus whilst ISR may be hijacked by viruses for facilitating its replication. In this review, we highlighted recent advances on induction of ISR upon viral infection and the downstream responses involved such as autophagy, apoptosis, formation of stress granules and innate immunity response. We then discussed the molecular mechanism of ISR regulating viral replication and how viruses antagonize this cellular stress response resulting from ISR.

Abstract A32: The role of the ribosome in GCN2's ability to sense amino acid deprivation and initiate the integrated stress response

2017 ◽  
Author(s):  
Alison J. Inglis ◽  
Sichen Shao ◽  
Glenn R. Masson ◽  
Olga Perisic ◽  
Ramanujan S. Hegde ◽  
...  
Keyword(s):  
Amino Acid ◽  
Stress Response ◽  
Integrated Stress Response ◽  
Amino Acid Deprivation

scholarly journals Regenerative Potential of Carbon Monoxide in Adult Neural Circuits of the Central Nervous System

2020 ◽  
Vol 21 (7) ◽  
pp. 2273
Author(s):  
Eunyoung Jung ◽  
Seong-Ho Koh ◽  
Myeongjong Yoo ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Carbon Monoxide ◽  
Nervous System ◽  
Neurotrophic Factors ◽  
Neural Circuits ◽  
Cns Injury ◽  
Cns Regeneration ◽  
The Central Nervous System ◽  
Endogenous Neural Stem Cells

Regeneration of adult neural circuits after an injury is limited in the central nervous system (CNS). Heme oxygenase (HO) is an enzyme that produces HO metabolites, such as carbon monoxide (CO), biliverdin and iron by heme degradation. CO may act as a biological signal transduction effector in CNS regeneration by stimulating neuronal intrinsic and extrinsic mechanisms as well as mitochondrial biogenesis. CO may give directions by which the injured neurovascular system switches into regeneration mode by stimulating endogenous neural stem cells and endothelial cells to produce neurons and vessels capable of replacing injured neurons and vessels in the CNS. The present review discusses the regenerative potential of CO in acute and chronic neuroinflammatory diseases of the CNS, such as stroke, traumatic brain injury, multiple sclerosis and Alzheimer’s disease and the role of signaling pathways and neurotrophic factors. CO-mediated facilitation of cellular communications may boost regeneration, consequently forming functional adult neural circuits in CNS injury.

scholarly journals Heme-regulated eIF2α kinase in erythropoiesis and hemoglobinopathies

Blood ◽  
2019 ◽  
Vol 134 (20) ◽  
pp. 1697-1707 ◽  
Author(s):  
Jane-Jane Chen ◽  
Shuping Zhang
Keyword(s):  
Protein Synthesis ◽  
Stress Response ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Iron Availability ◽  
Eukaryotic Initiation Factor ◽  
Erythroid Cells ◽  
Eif2α Kinase ◽  
In Erythroid Cells

Chen and Zhang review the role of eukaryotic initiation factor 2α (eIF2α) in regulating the balance between protein synthesis and iron availability as part of the integrated stress response in erythroid cells.

scholarly journals The Role of Astrocytes in the Central Nervous System Focused on BK Channel and Heme Oxygenase Metabolites: A Review

Antioxidants ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 121 ◽  
Author(s):  
Yonghee Kim ◽  
Jinhong Park ◽  
Yoon Kyung Choi
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Bk Channel ◽  
Cns Injury ◽  
Antioxidant Agents ◽  
The Central Nervous System

Astrocytes outnumber neurons in the human brain, and they play a key role in numerous functions within the central nervous system (CNS), including glutamate, ion (i.e., Ca2+, K+) and water homeostasis, defense against oxidative/nitrosative stress, energy storage, mitochondria biogenesis, scar formation, tissue repair via angiogenesis and neurogenesis, and synapse modulation. After CNS injury, astrocytes communicate with surrounding neuronal and vascular systems, leading to the clearance of disease-specific protein aggregates, such as β-amyloid, and α-synuclein. The astrocytic big conductance K+ (BK) channel plays a role in these processes. Recently, potential therapeutic agents that target astrocytes have been tested for their potential to repair the brain. In this review, we discuss the role of the BK channel and antioxidant agents such as heme oxygenase metabolites following CNS injury. A better understanding of the cellular and molecular mechanisms of astrocytes’ functions in the healthy and diseased brains will greatly contribute to the development of therapeutic approaches following CNS injury, such as Alzheimer’s disease, Parkinson’s disease, and stroke.

scholarly journals Integrated stress response restricts macrophage necroptosis

2021 ◽  
Vol 5 (1) ◽  
pp. e202101260
Author(s):  
David E Place ◽  
Parimal Samir ◽  
RK Subbarao Malireddi ◽  
Thirumala-Devi Kanneganti
Keyword(s):  
Cell Death ◽  
Stress Response ◽  
Cell Survival ◽  
Stress Responses ◽  
Critical Role ◽  
Stress Granule ◽  
Integrated Stress Response ◽  
Signaling Axis ◽  
Stressed Cells

The integrated stress response (ISR) regulates cellular homeostasis and cell survival following exposure to stressors. Cell death processes such as apoptosis and pyroptosis are known to be modulated by stress responses, but the role of the ISR in necroptosis is poorly understood. Necroptosis is an inflammatory, lytic form of cell death driven by the RIPK3-MLKL signaling axis. Here, we show that macrophages that have induced the ISR are protected from subsequent necroptosis. Consistent with a reduction in necroptosis, phosphorylation of RIPK1, RIPK3, and MLKL is reduced in macrophages pre-treated with ISR-inducing agents that are challenged with necroptosis-inducing triggers. The stress granule component DDX3X, which is involved in ISR-mediated regulation of pyroptosis, is not required for protecting ISR-treated cells from necroptosis. Disruption of stress granule assembly or knockdown of Perk restored necroptosis in pre-stressed cells. Together, these findings identify a critical role for the ISR in limiting necroptosis in macrophages.

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