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

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

Publication date: May 27, 2020

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 affected the activity of the ER stress response, and its downregulation removed the beneficial effect of itraconazole.

Our study revealed a new method for treating MS using currently approved antifungal drugs.

Concepts Keywords
AMPK Demyelination
Antifungal Experimental autoimmune encephalomyelitis
Antifungal Drug MS
Apoptosis Branches of biology
Autoimmune Medicine
Control Group Animal testing
Demyelination Experimental autoimmune encephalomyelitis
Downregulation Itraconazole
Endoplasmic Reticulum EAE
Eosin Apoptosis
ER Stress Apoptosis
Hematoxylin
Histology
Itraconazole
LFB
Multiple Sclerosis
Myelin
PBS
Staining
Stress
Stress Response
Western Blotting

Semantics

Type Source Name
drug DRUGBANK Itraconazole
disease MESH experimental autoimmune encephalomyelitis
disease MESH Multiple sclerosis
disease MESH autoimmune disease
drug DRUGBANK Phosphate ion
disease MESH demyelination
pathway KEGG Apoptosis

Original Article

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