Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic
Open accessAbstract
Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo , guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental autoimmune encephalomyelitis, guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS CD4+ T cell accumulation. Moreover, guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment.
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Greater than 95% pure cultures of rat oligodendrocyte progenitor cells (OPCs) were isolated.
“Greater than 95 % pure cultures of rat oligodendrocyte progenitor cells (OPCs) were isolated from cortices of 6–7 day old pups as described by sequential immunopanning on dishes coated with antibodies against Ran-2, GalC, and O4 [39].”
From Predominant expression of Alzheimer’s disease-associated BIN1 in mature oligodendrocytes and localization to white matter tracts (2016) · cites this paper as [39]
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“Interestingly, the pharmacological activation of ISR signaling with compounds that inhibit eIF2α dephosphorylation had beneficial effects in experimental models of many neurodegenerative disorders (Reijonen et al., 2008; Lee et al., 2010; Jiang et al., 2014; Das et al., 2015; Dash et al., 2015; Way et al., 2015), wher…”
BackgroundLei, Z., Yue, Y., Stone, S., Wu, S., & Lin, W. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.1156-20.2020 · Cited by 35 · see citing works
“Moreover, recent studies showed that treatment with small chemical compounds that enhance activation of the PERK-eIF2a pathway protects oligodendrocytes against inflammation during EAE (Way et al., 2015; Chen et al., 2019).”
BackgroundProlonging the integrated stress response enhances CNS remyelination in an inflammatory environment
Chen, Y.-N., Kunjamma, R. B., Weiner, M., Chan, J., & Popko, B. (2020) · bioRxiv · doi:10.1101/2020.12.29.424699 · Cited by 31
Self-citationYang, Z.-Y., Shi, L., Wang, Y., Zhou, D., Zhang, C., & Lin, Y.-F. (2024) · Small · doi:10.1002/smll.202410162 · Cited by 29
Neuronal microRNA regulation in Experimental Autoimmune Encephalomyelitis
Juźwik, C. A., Drake, S. S., Lécuyer, M.-A., Johnson, R. M., Morquette, B., Zhang, Y., Charabati, M., Sagan, S., Bar-Or, A., Prat, A., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-31542-y · Cited by 29 · see citing works
Wright, G. E. B., Caron, N. S., Ng, B., Casal, L. L., Casazza, W., Xu, X., Ooi, J., Pouladi, M. A., Mostafavi, S., Ross, C. J., et al. (2020) · Human Molecular Genetics · doi:10.1093/hmg/ddaa184 · Cited by 31 · see citing works
“These include chro-momycin, which has been proposed as a potential therapeutic target for neurological disorders caused by repeat expansions (42), as well as mitoxantrone and guanabenz, which have been implicated as potential medications for multiple sclerosis (43,44).”
Perego, J., Mendes, A. V., Bourbon, C., Camosseto, V., Combes, A. J., Liu, H., Manh, T. V., Dalet, A., Chasson, L., Spinelli, L., et al. (2018) · Science Signaling · doi:10.1126/scisignal.aam8104 · Cited by 25 · see citing works
“Despite conflicting results (22, 31, 32), these mouse experiments have yielded important pharmacokinetics data on GBZ, including a plasma half-life of 1.”
BackgroundResultZuroff, L. R., Farkhondeh, V., Bove, R. M., & Green, A. (2025) · Drugs · doi:10.1007/s40265-025-02212-x · Cited by 18 · see citing works
“Whether supporting oligodendrocyte survival in isolation might yield a neuroprotective benefit remains to be fully explored [42, 43].”
Mechanisms Governing Oligodendrocyte Viability in Multiple Sclerosis and Its Animal Models
Lei, Z., & Lin, W. (2024) · Cells · doi:10.3390/cells13020116 · Cited by 23 · see citing works
“…promise of selective inhibitors targeting GADD34, Guanabenz and Sephin1, in MS. Treatment with these inhibitors increases p-eIF2 α levels in oligodendrocytes, resulting in decreased disease severity and an improvement in oligodendrocyte survival and myelin damage in the EAE model [114,115].”
BackgroundIntegrated Stress Response as a Therapeutic Target for CNS Injuries
Romero-Ramírez, L., Nieto-Sampedro, M., & Barreda-Manso, M. A. (2017) · BioMed Research International · doi:10.1155/2017/6953156 · Cited by 23 · see citing works
“In particular, guanabenz was cytoprotective for oligodendrocytes and reduced demyelination [75].”
BackgroundOligodendrocyte-specific ATF4 inactivation does not influence the development of EAE
Yue, Y., Stanojlović, M., Lin, Y., Karsenty, G., & Lin, W. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1415-6 · Cited by 23 · see citing works
Li, T., Yang, S., She, X., Yan, Q., Zhang, P., Zhu, H., Wang, F., Luo, X., & Sun, X. (2018) · British Journal of Pharmacology · doi:10.1111/bph.14565 · Cited by 28 · see citing works
“Moreover, different types of ARs have been shown to be implicated in inflammatory responses within various injury models (Tung et al., 2013; Way et al., 2015).”
BackgroundMethodInfluentialFSD-C10, a Fasudil derivative, promotes neuroregeneration through indirect and direct mechanisms
Lǐ, Y., Xie, C., Zhang, Y., Li, X., Zhang, H., Wang, Q., Chai, Z., Xiao, B., Thomé, R., Zhang, G., et al. (2017) · Scientific Reports · doi:10.1038/srep41227 · Cited by 23 · see citing works
Differential activation of ER stress pathways in myelinating cerebellar tracts
Naughton, M., McMahon, J., & Fitzgerald, U. (2015) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2015.08.002 · Cited by 20
Guanabenz Downregulates Inflammatory Responses via eIF2α Dependent and Independent Signaling
Takigawa, S., Chen, A. B., Nishimura, A., Liu, S., Li, B., Sudo, A., Yokota, H., & Hamamura, K. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050674 · Cited by 22 · see citing works
“Recently guanabenz has been reported to have a potential therapeutic effect for multiple sclerosis, which is an inflammatory disease associated with oligodendrocyte death in the central nervous system [12].”
BackgroundResultChen, Y., Quan, S., Patil, V., Kunjamma, R. B., Tokars, H. M., Leisten, E. D., Joy, G., Wills, S., Chan, J. R., Wong, Y. C., et al. (2023) · Glia · doi:10.1002/glia.24386 · Cited by 21 · see citing works
“by the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2α) (Pakos-Zebrucka et al., 2016; Way et al., 2015; Way & Popko, 2016).”
BackgroundMethodSelf-citationCallejo, G., Pattison, L. A., Greenhalgh, J., Chakrabarti, S., Andreopoulou, E., Hockley, J. R. F., Smith, E. S. J., & Rahman, T. (2019) · bioRxiv · doi:10.1101/704445 · Cited by 17
Guanabenz Prevents d-Galactosamine/Lipopolysaccharide-Induced Liver Damage and Mortality
Perego, J., Bourbon, C., Chasson, L., Laprie, C., Spinelli, L., Camosseto, V., Gatti, E., & Pierre, P. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00679 · Cited by 19 · see citing works
Hypoxic Neuroinflammation in the Pathogenesis of Multiple Sclerosis
Hollingworth, B. Y. A., Pallier, P., Jenkins, S., & Chen, R. (2025) · Brain Science · doi:10.3390/brainsci15030248 · Cited by 16 · see citing works
“It prevents myelin loss and increases oligodendrocyte survival as well as reduces deficits in the EAE model [108].”
Guanabenz modulates microglia and macrophages during demyelination
Thompson, K. K., & Tsirka, S. E. (2020) · Scientific Reports · doi:10.1038/s41598-020-76383-w · Cited by 17 · see citing works
Sephin1 Reduces Prion Infection in Prion-Infected Cells and Animal Model
Thapa, S., Abdelaziz, D. H., Abdulrahman, B., & Schätzl, H. M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-01880-y · Cited by 16 · see citing works
Chen, X., Xie, Y., Liu, Z., & Lin, Y. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.782237 · Cited by 15 · see citing works
The remyelination effect of DNA framework nucleic acids on demyelinating diseases
Yang, Y., Zhu, J., Ma, W., Zhang, W., Xie, Y., Chen, X., Zhu, J., Liu, Y., Qin, X., & Lin, Y. (2021) · Applied Materials Today · doi:10.1016/j.apmt.2021.101098 · Cited by 16 · see citing works
Guanabenz Attenuates Acetaminophen-Induced Liver Toxicity and Synergizes Analgesia in Mice
Xie, W., Xie, J., Vince, R., & More, S. S. (2019) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.9b00162 · Cited by 14 · see citing works
White Matter in Crisis: Oligodendrocytes and the Pathophysiology of Multiple Sclerosis
García-Domínguez, M. (2025) · Cells · doi:10.3390/cells14181408 · Cited by 13 · see citing works
Sephin1 Protects Neurons against Excitotoxicity Independently of the Integrated Stress Response
Ruiz, A., Zuazo, J., Ortiz-Sanz, C., Luchena, C., Matute, C., & Alberdi, E. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176088 · Cited by 13
“The hypotensive drug guanabenz [13] enhances the ISR by inhibiting GADD34 [14] and protects neurons and oligodendrocytes in models of Parkinson ́s disease and multiple sclerosis, respectively [15,16].”
BackgroundThe Integrated Stress Response in Hypoxia-Induced Diffuse White Matter Injury
Clayton, B. L. L., Huang, A., Kunjamma, R. B., Solanki, A., & Popko, B. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.2738-16.2017 · Cited by 13 · see citing works
“Effects of genetic enhancement of the ISR on MCH- and SAH-induced DWMI Inhibition of Gadd34 has been shown to protect oligodendrocytes in mouse models of multiple sclerosis (Lin et al., 2008; Way et al., 2015).”
BackgroundMethodInfluentialSelf-citationWu, Y., Zhang, H., Wang, Y., Zhang, Y., Hong, Z.-Y., & Wang, D. (2024) · Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · doi:10.1016/j.biopha.2024.116869 · Cited by 12
hnRNP A1 dysfunction in oligodendrocytes contributes to the pathogenesis of multiple sclerosis
Jahan-Abad, A. J., Salapa, H. E., Libner, C. D., Thibault, P., & Levin, M. (2022) · Glia · doi:10.1002/glia.24300 · Cited by 12 · see citing works
“Furthermore, pro-inflammatory cytokines, such as IFNγ, have been shown to contribute to OL death in MS and relevant models (Lin et al., 2005; Pouly et al., 2000; Vartanian et al., 1995; Way et al., 2015).”
BackgroundLuo, F., Zhang, Z., & Luo, Y. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312811 · Cited by 12 · see citing works
“In addition to enhancing OL differentiation and myelin repair, experimental studies demonstrate that the protective strategy of OLs and myelin can provide complementary effects in alleviating disease progression [2].”
BackgroundHoch-Kraft, P., Trotter, J., & Gonsior, C. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02763-y · Cited by 9 · see citing works
Jiang, M.-Q., Rao, R., Wang, J.-C., Wang, J.-J., Xu, L.-L., Wu, L.-M., Chan, J. R., Wang, H.-M., & Lu, Q. R. (2018) · Glia · doi:10.1002/glia.23449 · Cited by 10 · see citing works
“Although the molecular mechanisms underlying distinct phenotypes in the central and peripheral nervous systems remain to be elucidated, elevation of adaptive responses mediated by p-eIF2a (Jiang et al., 2016; Way et al., 2015) in Tsc1-mutant SCs (Supporting Information Figure S2) and strong upregulation of the SC prol…”
BackgroundISR Modulators in Neurological Diseases
Kalinin, A., Zubkova, E., Menshikov, M., & Parfyonova, Y. (2025) · Current Neuropharmacology · doi:10.2174/011570159x361653250213114821 · Cited by 12 · see citing works
“The authors observed that the guanabenz-mediated enhancement of the ISR is sufficient to protect oligodendrocytes from in-flammation-induced loss [160].”
InfluentialMakar, T. K., Guda, P. R., Ray, S., Andhavarapu, S., Keledjian, K. M., Gerzanich, V., Simard, J. M., Nimmagadda, V. K. C., & Bever, C. T. (2023) · Scientific Reports · doi:10.1038/s41598-023-29852-x · Cited by 13 · see citing works
“Other chemical compounds that have been shown to activate this pathway and are neuroprotective in EAE and MS include salburnal [70] and guanabenz [71].”
BackgroundThe future of multiple sclerosis treatments
Coclitu, C., Constantinescu, C. S., & Tănăsescu, R. (2016) · Expert Review of Neurotherapeutics · doi:10.1080/14737175.2016.1243056 · Cited by 10 · see citing works
Dooves, S., Bugiani, M., Wisse, L., Abbink, T., van der Knaap, M. S., & Heine, V. (2017) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12411 · Cited by 8 · see citing works
Chen, Y., Kunjamma, R. B., Lin, K., Li, K., Dima, M., Bruce, K., Steckler, I., Hyun, Y. S., Chan-Zervas, J., von Bernhardi, J. E., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-68045-0 · Cited by 10 · see citing works
Self-citationInhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis
Ding, Z.-B., Chen, Y., Zheng, Y., Wang, Y., Deng, W., Zheng, J.-H., Yang, Q., Chen, Z.-Y., Li, L., Jiang, H., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01209-0 · Cited by 7 · see citing works
“…of Sephin1 ’ s precise mode of action, its presence clearly results in prolonged and elevated levels of phosphorylated eIF2 α in stressed cells, and this phenomenon minimizes any concerns about deleterious effects on unstressed cells since they only affect cells under cytotoxic stress [16, 49].”
News in multiple sclerosis: Remyelination as a therapeutic target.
Matías-Guíu, J., Gómez-Pinedo, U., & Matias-Guiu, J. (2017) · Medicina clínica (Ed. impresa) · doi:10.1016/j.medcli.2016.10.021 · Cited by 6 · see citing works
GCN2-Mediated eIF2α Phosphorylation Is Required for Central Nervous System Remyelination
Falcón, P., Brito, Á., Escandón, M., Roa, J. F., Martínez, N. W., Tapia-Godoy, A., Farfán, P., & Matus, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26041626 · Cited by 7 · see citing works
“Since oligodendrocytes are the primary responders to demyelination-related stress, playing a crucial role in maintaining myelin integrity [30,54,55], part of the phenotype observed here could be due to the contribution of GCN2 in oligodendrocytes, but we cannot discard the contribution of another…”
Amatruda, M., Harris, K., Matis, A., Davies, A., Mcelroy, D., Clark, M., Linington, C., Desai, R. A., & Smith, K. J. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12868 · Cited by 5 · see citing works
“feature makes the passive EAE model a valuable tool to assess whether the efficacy of a treatment relies or not on the priming of the autoimmune response [57, 58].”
BackgroundEslami, A., Dehbashi, M., Ashja‐Arvan, M., Salehi, H., Azimzadeh, M., & Ganjalıkhani-Hakemi, M. (2020) · Cytotechnology · doi:10.1007/s10616-020-00421-8 · Cited by 5 · see citing works
Claes, Z., Jonkhout, M. C. M., Crespillo-Casado, A., & Bollen, M. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.008857 · Cited by 5
“Guanabenz, sephin1, and raphin1 have shown promising results in various murine models of neurodegenerative diseases (10, 11, 18).”
BackgroundThe role of the unfolded protein response in myelination
Naughton, M., McMahon, J., & Fitzgerald, U. (2016) · Neural Regeneration Research · doi:10.4103/1673-5374.179036 · Cited by 5
“…known to stimulate the PERK-EIF2 α arm of the UPR, to cultured oligodendrocytes and cerebellar explants produced oligodendrocyte-protective effects similar to those achieved by stimulating PERK (Way et al., 2015) and has led to the proposition that the drug could be a potential therapeutic for MS.”
A comparative transcriptomic analysis of mouse demyelination models and multiple sclerosis lesions
Aboelnour, E. L., Vanoverbeke, V. R., Maupin, E. A., Hatfield, M. M., & Adams, K. L. (2026) · Nature Communications · doi:10.1038/s41467-026-72383-y · Cited by 4 · see citing works
Zhan, J., Gao, Y., Heinig, L., Beecken, M., Huo, Y., Zhang, W., Wang, P., Wei, T., Tian, R., Han, W., et al. (2023) · Cells · doi:10.3390/cells12162085 · Cited by 6 · see citing works
“Our results show that the knockdown of Cmtm5 has no effect on the induction of Atf4, an activator of cytoprotective responses under cellular stress conditions [21] (Figure 3c: Cmtm5, non-targeting control DMSO treated 96.”
BackgroundResultLin, M. L., & Lin, W. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27041779 · Cited by 2 · see citing works
“Moreover, pharmacological agents such as Guanabenz and Sephin1, which inhibit dephosphorylation of phosphorylated eIF2 α , enhance the activity of the PERK-eIF2 α pathway in oligodendrocytes and ameliorate EAE severity, oligodendrocyte loss and demyelination [69,70].”
AA147 Alleviates Symptoms in a Mouse Model of Multiple Sclerosis by Reducing Oligodendrocyte Loss
Aksu, M., Kaschke, K., Podojil, J. R., Chiang, M., Steckler, I., Bruce, K., Cogswell, A. C., Schulz, G., Kelly, J. W., Wiseman, R. L., et al. (2025) · Glia · doi:10.1002/glia.70001 · Cited by 4 · see citing works
“Small molecules that selectively prolong the PERK branch activation of the UPR, such as Guanabenz and its derivative Sephin1, have been found to delay EAE disease onset and reduce oligodendrocyte death (Way et al. 2015; Chen et al. 2019, 2023).”
Self-citationThe translation initiation factor eIF2α regulates lipid homeostasis and metabolic aging
Huang, H., Liao, Y., Li, N., Qu, X., Li, C., & Hou, J. (2024) · Aging Cell · doi:10.1111/acel.14348 · Cited by 3 · see citing works
“Moreover, the beneficial effects of ISR inhibition were reported in Huntington's disease (Krzyzosiak et al., 2018), ALS (Das et al., 2015), and multiple sclerosis (Way et al., 2015).”
Lin, H., Naveed, M., Hansen, A., Anthony, T. G., & Cao, R. (2023) · Clocks & Sleep · doi:10.3390/clockssleep5040043 · Cited by 3 · see citing works
“The dose was determined based on a previous study indicating that 4–16 mg/kg treatment with guanabenz in mice would likely achieve CNS levels sufficient to modulate the ISR [28].”
MethodChen, Y.-N., Quan, S.-H., Patil, V., Kunjamma, R. B., Tokars, H. M., Leisten, E. D., Chan, J., Wong, Y., & Popko, B. (2023) · bioRxiv · doi:10.1101/2023.01.23.525156 · Cited by 3
“To cope with inflammatory stress, an innate cytoprotective response called the integrated stress response (ISR) is triggered in oligodendrocytes, centered by the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2a) (Pakos-Zebrucka et al., 2016; Way and Popko, 2016; Way et al., 2015).”
BackgroundSelf-citationHe, W., Liu, X., Wang, D., Gong, Y., Cui, T., Zhang, X., Li, P., Ding, X.-L., Yang, L.-T., Zhang, Q., et al. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03640-y · Cited by 2 · see citing works
“Pharmacological upregulation of the integrated stress response (e.g. with guanabenz, which prolongs PERK pathway signaling) likewise preserved oligodendrocyte viability and alleviated clinical EAE severity, pointing to the therapeutic potential of targeting this pathway [19– 21].”
Traditional medicine meets modern science: Halofuginone’s role in combating autoimmune diseases
Zhu, J., Liu, S., Liu, P., Zhai, K.-F., & Liu, H. (2025) · Journal of Natural Medicines · doi:10.1007/s11418-025-01927-1 · Cited by 2 · see citing works
“Immune-mediated oligodendrocyte loss as a mechanism contributes to the pathogenesis of MS [37, 38].”
News in multiple sclerosis: Remyelination as a therapeutic target
Matías-Guíu, J., Gómez-Pinedo, U., & Matias-Guiu, J. (2017) · Medicina Clínica (English Edition) · doi:10.1016/j.medcle.2017.04.008 · Cited by 2 · see citing works
Pharmacological targeting of endoplasmic reticulum stress in disease
Marciniak, S., Chambers, J. E., & Ron, D. (2021) · Nature reviews. Drug discovery · doi:10.1038/s41573-021-00320-3 · Cited by 1 · see citing works
Wang, L., Duan, X., Liu, H., Lin, F., Zhou, C., Schröder, K., Shah, A., Zhao, G., & Zhang, M. (2025) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2025.101433 · Cited by 1 · see citing works
Sephin1 alleviates white matter injury by protecting oligodendrocyte after intracerebral hemorrhage
Liu, F., Ma, Q.-Q., Li, X.-H., Li, Z.-Q., Wang, P., Yang, W.-S., Shen, Y., Li, P.-Z., Pu, M., Xiao, Z., et al. (2025) · bioRxiv · doi:10.1177/0271678x261437531 · Cited by 1 · see citing works
“44 Therefore, these findings support the idea that Sephin1 exerts effects by modulating the ISR of stressed cells surrounding the hematoma, including OLs, microglia, astrocytes, and neurons, rather than specifically focusing on OLs.”
The Role of the Integrated Stress Response (ISR) in Neuropsychiatric Disorders
Ilyin, N. P., Nikitin, V. S., & Kalueff, A. V. (2024) · Journal of Evolutionary Biochemistry and Physiology · doi:10.1134/s002209302406005x · Cited by 2 · see citing works
“…[124] Guanabenz increases p-eIF2 α , reduces interferon-γ -induced oligodendrocyte loss and demyelination in cell culture and mouse models of MS [131] Traumatic Brain Injury (TBI) ↑ p-eIF2 α , p-PERK, ATF4, and other UPR markers in various brain regions in mouse and rat models of TBI [46, 132–”
Mechanisms and therapeutic strategies for central and peripheral remyelination
Zhan, J., Jo, J., Cristobal, C. D., Jeong, D. J., Park, H. T., & Lee, H. K. (2026) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2026.102964
- Authors
- Way, S. W., Podojil, J. R., Clayton, B. L., Zaremba, A., Collins, T. L., Kunjamma, R. B., Robinson, A. P., Brugarolas, P., Miller, R. H., Miller, S. D., & Popko, B.
- Affiliations
- University of Chicago (US)
- Northwestern University (US)
- Case Western Reserve University (US)
- Myelin Repair Foundation (US)
- Corresponding author
- Popko, Brian
- ORCID
- Venue
- Nature Communications
- Published
- 2015-03-13
- Volume
- 6
- Issue
- 1
- Pages
- 6532-6532
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC4360920
- OpenAlex
- W2068319964
- Cited by
- 108
- References
- 59
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 9 · 2018: 13 · 2017: 11 · 2016: 11 · 2015: 8
- FWCI
- 11.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Multiple Sclerosis Society (FG 1998-A-1)
- Myelin Repair Foundation
- Multiple Sclerosis Society
- National Institutes of Health (UL1TR000430, NS34939)
- National Institute of Neurological Disorders and Stroke (NS34939, R01NS034939, R01NS026543)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- integrated stress response, guanabenz, oligodendrocyte survival, multiple sclerosis, interferon-gamma, demyelination, experimental autoimmune encephalomyelitis, relapsing-remitting multiple sclerosis, CD4+ T cells, neuroprotection
- MeSH terms
- Animals, Cell Differentiation, Cell Survival, Cells, Cultured, Central Nervous System, Cerebellum, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental, Female, Guanabenz, Inflammation, Interferon-gamma, Mice, Inbred C57BL, Multiple Sclerosis, Myelin Sheath, Oligodendroglia, Stem Cells, CD4-Positive T-Lymphocytes, Cytokines, Rats, Sprague-Dawley, Disease Progression, Mice, Rats
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