ArticleJournal of neuroinflammation2019
Oligodendrocyte-specific ATF4 inactivation does not influence the development of EAE.
Article in Journal of neuroinflammation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Oligodendrocytes Are Active Participants in the Pathogenesis of Multiple Sclerosis and Its Animal Models.International journal of molecular sciences · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- The integrated stress response in neurodegenerative diseases.Molecular neurodegeneration · 2025Review
- Mechanism analysis and intervention strategies of the inflammatory microenvironment in traumatic spinal cord injury.Frontiers in immunology · 2025Review
- Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models.Cells · 2024Review
- Endoplasmic reticulum associated degradation preserves neurons viability by maintaining endoplasmic reticulum homeostasis.Frontiers in neuroscience · 2024Article
- The PERK pathway: beneficial or detrimental for neurodegenerative diseases and tumor growth and cancer.Human molecular genetics · 2023Review
- The UPR Maintains Proteostasis and the Viability and Function of Hippocampal Neurons in Adult Mice.International journal of molecular sciences · 2023Article
- Acute Pharmacological Inhibition of Protein Kinase R-Like Endoplasmic Reticulum Kinase Signaling After Spinal Cord Injury Spares Oligodendrocytes and Improves Locomotor Recovery.Journal of neurotrauma · 2023Article
- Endoplasmic Reticulum Stress in Elderly Patients with COVID-19: Potential of Melatonin Treatment.Viruses · 2023Review
- Detection of PERK Signaling in the Central Nervous System.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Endoplasmic Reticulum Stress-Associated Neuronal Death and Innate Immune Response in Neurological Diseases.Frontiers in immunology · 2021Review
- NF-κB Activation Accounts for the Cytoprotective Effects of PERK Activation on Oligodendrocytes during EAE.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Crosstalk between ER stress, NLRP3 inflammasome, and inflammation.Applied microbiology and biotechnology · 2020Review
- Unfolded protein response in myelin disorders.Neural regeneration research · 2020Review
- Effects of Retinal Transcription Regulation After GB20 Needling Treatment in Retina With Optic Neuritis.Frontiers in integrative neuroscience · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMultiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory demyelinating and neurodegenerative diseases of the CNS. Although recent studies suggest the neuroprotective effects of oligodendrocytes in neurodegenerative diseases, it remains unknown whether oligodendrocyte death induced by inflammatory attacks contributes to neurodegeneration in MS and EAE. Upon endoplasmic reticulum (ER) stress, activation of pancreatic ER kinase (PERK) promotes cell survival through induction of activating transcription factor 4 (ATF4) by phosphorylating eukaryotic translation initiation factor 2α (eIF2α). We have generated a mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. Our previous study has demonstrated that PERK activation specifically in oligodendrocytes attenuates EAE disease severity and ameliorates EAE-induced oligodendrocyte apoptosis, demyelination, and axon degeneration, without altering inflammation.
methodsWe determined whether oligodendrocyte-specific PERK activation reduced neuron loss in the CNS of EAE mice using the mouse model that allows for temporally controlled activation of PERK specifically in oligodendrocytes. We further generated a mouse model that allows for inactivation of ATF4 specifically in oligodendrocytes, and determined the effects of ATF4 inactivation in oligodendrocytes on mice undergoing EAE.
resultsWe showed that protection of oligodendrocytes resulting from PERK activation led to attenuation of neuron loss in the CNS gray matter of EAE mice. Surprisingly, we found that ATF4 inactivation specifically in oligodendrocytes did not alter EAE disease severity and had no effect on oligodendrocyte loss, demyelination, axon degeneration, neuron loss, and inflammation in EAE mice.
conclusionsThese findings suggest the neuroprotective effects of PERK activation in oligodendrocytes in EAE, and rule out the involvement of ATF4 in oligodendrocytes in the development of EAE. These results imply that the protective effects of PERK activation in oligodendrocytes in MS and EAE are not mediated by ATF4.
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Registered trials
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