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Repurposing of Secukinumab as Neuroprotective in Cuprizone-Induced Multiple Sclerosis Experimental Model via Inhibition of Oxidative, Inflammatory, and Neurodegenerative Signaling

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Abstract

Multiple sclerosis (MS) is a chronic, inflammatory, and neurodegenerative autoimmune disease. MS is a devastating disorder that is characterized by cognitive and motor deficits. Cuprizone-induced demyelination is the most widely experimental model used for MS. Cuprizone is a copper chelator that is well characterized by microgliosis and astrogliosis and is reproducible for demyelination and remyelination. Secukinumab (SEC) is a fully human monoclonal anti-human antibody of the IgG1/kappa isotype that selectively targets IL-17A. Expression of IL-17 is associated with MS. Also, IL-17 stimulates microglia and astrocytes resulting in progression of MS through chemokine production and neutrophil recruitment. This study aimed to investigate the neuroprotective effects of SEC on cuprizone-induced demyelination with examining the underlying mechanisms. Locomotor activity, short-term spatial memory function, staining by Luxol Fast Blue, myelin basic protein, gliasosis, inflammatory, and oxidative-stress markers were assessed to evaluate neuroprotective, anti-inflammatory and antioxidant effects. Moreover, the safety profile of SEC was evaluated. The present study concludes the efficacy of SEC in Cup-induced demyelination experimental model. Interestingly, SEC had neuroprotective and antioxidant effects besides its anti-inflammatory effect in the studied experimental model of MS.

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Authors and Affiliations

  1. National Organization for Research and Control of Biologicals (NORCB), Cairo, Egypt

    Amany El-Shahawy Abdel-Maged

  2. Department of Pharmacology, National Organization for Drug Control and Research (NODCAR), Cairo, Egypt

    Amany M. Gad

  3. Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Cairo, Egypt

    Laila Ahmed Rashed

  4. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt

    Samar S. Azab

  5. Departmentof Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

    Eman A. Mohamed & Azza S. Awad

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  1. Amany El-Shahawy Abdel-Maged
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Correspondence to Samar S. Azab.

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Highlights

• SEC elicited neuroprotective effect in MS model

• SEC improved behavioral and neurobiochemical markers

• SEC produced antioxidant and anti-inflammatory effects

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Abdel-Maged, A.ES., Gad, A.M., Rashed, L.A. et al. Repurposing of Secukinumab as Neuroprotective in Cuprizone-Induced Multiple Sclerosis Experimental Model via Inhibition of Oxidative, Inflammatory, and Neurodegenerative Signaling. Mol Neurobiol 57, 3291–3306 (2020). https://doi.org/10.1007/s12035-020-01972-9

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