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Volume 25
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10.3390/ijms252212035
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Article

Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction

by
Yanjia Shen
,
Jiaying Zhao
,
Ran Yang
,
Huilin Yang
,
Minmin Guo
,
Baixi Ji
,
Guanhua Du
and
Li Li
*
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(22), 12035; https://doi.org/10.3390/ijms252212035
Submission received: 20 September 2024 / Revised: 17 October 2024 / Accepted: 4 November 2024 / Published: 9 November 2024
(This article belongs to the Special Issue Natural Products and Synthetic Compounds for Drug Development 2.0)
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Abstract

Multiple sclerosis (MS) is an autoimmune disease mediated by T helper cells, which is characterized by neuroinflammation, axonal or neuronal loss, demyelination, and astrocytic gliosis. Histone deacetylase inhibitors (HDACis) are noted for their roles in easing inflammatory conditions and suppressing the immune response. Panobinostat, an HDACi, is now being used in treating multiple myeloma. Nevertheless, the effect of panobinostat on autoimmune diseases remains largely unclear. Thus, our research endeavored to determine if the administration of panobinostat could prevent experimental autoimmune encephalomyelitis (EAE) in mice, one of the most commonly used animal models of MS, and further explored the underlying mechanisms. The EAE mice were generated and then administered continuously with panobinostat at a dosage of 30 mg/kg for 16 days. The results indicated that panobinostat markedly alleviated the clinical symptoms of EAE mice, inhibiting demyelination and loss of oligodendrocytes in the central nervous system (CNS). Moreover, panobinostat decreased inflammation and the activation of microglia and astrocytes in the spinal cords of EAE mice. Mechanistically, treatment with panobinosat significantly suppressed M1 microglial polarization by blocking the activation of toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (MyD88)/interferon regulatory factor 5 (IRF5) pathway. Additionally, panobinostat inhibited mitochondrial dysfunction and reduced oxidative stress in the spinal cords of EAE mice. In conclusion, our findings reveal that panobinostat significantly ameliorates experimental autoimmune encephalomyelitis in mice by inhibiting oxidative stress-linked neuroinflammation and mitochondrial dysfunction.
Keywords: panobinostat; multiple sclerosis; experimental autoimmune encephalomyelitis; neuroinflammation; mitochondrial dysfunction; oxidative stress panobinostat; multiple sclerosis; experimental autoimmune encephalomyelitis; neuroinflammation; mitochondrial dysfunction; oxidative stress

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MDPI and ACS Style

Shen, Y.; Zhao, J.; Yang, R.; Yang, H.; Guo, M.; Ji, B.; Du, G.; Li, L. Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction. Int. J. Mol. Sci. 2024, 25, 12035. https://doi.org/10.3390/ijms252212035

AMA Style

Shen Y, Zhao J, Yang R, Yang H, Guo M, Ji B, Du G, Li L. Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction. International Journal of Molecular Sciences. 2024; 25(22):12035. https://doi.org/10.3390/ijms252212035

Chicago/Turabian Style

Shen, Yanjia, Jiaying Zhao, Ran Yang, Huilin Yang, Minmin Guo, Baixi Ji, Guanhua Du, and Li Li. 2024. "Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction" International Journal of Molecular Sciences 25, no. 22: 12035. https://doi.org/10.3390/ijms252212035

APA Style

Shen, Y., Zhao, J., Yang, R., Yang, H., Guo, M., Ji, B., Du, G., & Li, L. (2024). Panobinostat Attenuates Experimental Autoimmune Encephalomyelitis in Mice via Suppressing Oxidative Stress-Related Neuroinflammation and Mitochondrial Dysfunction. International Journal of Molecular Sciences, 25(22), 12035. https://doi.org/10.3390/ijms252212035

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