May 28, 2020

Antifungal itraconazole ameliorates experimental autoimmune encephalomyelitis through a novel mechanism of action

Advances in Clinical and Experimental Medicine : Official Organ Wroclaw Medical University
Huifen HuangXueli Cai

Abstract

Multiple sclerosis (MS) is an autoimmune disease characterized by a loss of myelin, limb disabilities and dysregulation of gene expression. Unfortunately, there still is no treatment to cure MS. To explore a novel way to treat MS using currently available antifungal drugs. We built an experimental autoimmune encephalomyelitis (EAE) model to mimic MS and tested the effect of an antifungal drug - itraconazole - on EAE by comparing it with a phosphate-buffered saline (PBS) control group. We assessed the animal limb deficits with Weaver's scoring and used histology staining (including luxol fast blue (LFB) and hematoxylin & eosin (H&E) methods) to determine the demyelination in the spinal tissues. We also performed western blotting to quantify the expression changes of proteins related to endoplasmic reticulum (ER) stress response and apoptosis. The limb disabilities were greatly diminished and the demyelination in the spinal tissues of the EAE mice was mostly reduced following itraconazole treatment. The hyperactivation of the ER stress response and apoptosis pathway in EAE was also significantly diminished by the itraconazole treatment. In addition, the AMPK pathway was downregulated in EAE, its expression level bi-directionally ...Continue Reading

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Mentioned in this Paper

Myelin Proteins
Multiple Sclerosis
Autoimmune Diseases
Antibiotics, Antifungal
Biological Adaptation to Stress
Demyelination
Protein Expression
Response to Endoplasmic Reticulum Stress
Limb Structure
Laboratory mice

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