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bioRxiv · 10.1101/2021.05.04.442578

Immunomodulatory Therapy with Glatiramer Acetate Reduces Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis

Makar, T.·Guda, P. R.·Ray, S.·Andhavarapu, S.·Nimmagadda, V. K.·Gerzanich, V.·Simard, J. M.·Bever, C. T.
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Abstract

Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are found in lesions of multiple sclerosis (MS) and of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and may contribute to the neuronal loss that underlies permanent impairment. These pathological changes are due to the neuroinflammation that characterizes MS and the strong interplay between the ER and mitochondria. We investigated whether immunomodulatory drug glatiramer acetate (GA) can reduce these changes in the spinal cords of chronic EAE mice by using routine histology, immunostaining, and electron microscopy. EAE spinal cord tissue exhibited increased infiltration/inflammation (upregulation of proinflammatory cytokines), demyelination, mitochondrial dysfunction (increased fission, decreased fusion, and increased biogenesis), ER stress, downregulation of NAD+ dependent pathways, and increased neuronal death. GA reversed these pathological changes, suggesting that immunomodulating therapy can attenuate ER stress, mitochondrial dysfunction, apoptotic cell death, and demyelination in the CNS and increase NAD+ utilizing activities by suppressing neuroinflammation.

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Makar, T., Guda, P. R., Ray, S., Andhavarapu, S., Nimmagadda, V. K., Gerzanich, V., Simard, J. M., Bever, C. T.. 2021-05-04. Immunomodulatory Therapy with Glatiramer Acetate Reduces Endoplasmic Reticulum Stress and Mitochondrial Dysfunction in Experimental Autoimmune Encephalomyelitis. https://doi.org/10.1101/2021.05.04.442578

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