Myelin is a protective sheath surrounding nerves. Damage to this covering -- demyelination -- is a hallmark of multiple sclerosis and related diseases of the central nervous system.

"We see this as an exciting finding, suggesting a new avenue in the search for therapies to correct the ravages of MS and other demyelinating diseases," said the paper's senior author, Subramaniam Sriram, MBBS, William C. Weaver III Professor of Neurology and chief of the Division of Neuroimmunology.

Previous work led by Sriram showed that a protein called interleukin 33, or IL-33, induced myelin formation. IL-33 is, among other things, an immune response regulator, and multiple sclerosis is an autoimmune disorder.

The cashew shell compound is called anacardic acid. Sriram and team grew interested in it because it's known to inhibit an enzyme involved in gene expression called histone acetyltransferase, or HAT, and the team had discovered that whatever inhibits HAT induces production of IL-33.

The report includes a range of new findings that point to potential therapeutic use of anacardic acid for demyelinating diseases:

• In vitro, the addition of the compound to rat cells most responsible for myelination -- oligodendrocyte precursor cells, or OPCs -- spurred induction of IL-33 and rapidly increased the expression of myelin genes and proteins, including dose-dependent increases in myelin basic protein;
• In two animal models of demyelination, treatment with the compound increased the relative presence of IL-33-expressing OPCs and led to reduced paralysis;
• In an animal model of demyelination treated with the compound, dissection and electron microscopy showed dose-dependent increases in myelination.

"These are striking results that clearly urge further study of anarcardic acid for demyelinating diseases," Sriram said.

Joining Sriram for the study were Asa Ljunggren-Rose, Chandramohan Natarajan, Pranathi Matta, Akansha Pandey and Isha Upender.

Story Source:

Materials provided by Vanderbilt University Medical Center. Original written by Paul Govern. Note: Content may be edited for style and length.

Journal Reference:

1. Åsa Ljunggren-Rose, Chandramohan Natarajan, Pranathi Matta, Akansha Pandey, Isha Upender, and Subramaniam Sriram. Anacardic acid induces IL-33 and promotes remyelination in CNS. PNAS, 2020 DOI: 10.1073/pnas.2006566117