Anacardic acid, interleukin-33, and the quest for remyelination

In PNAS, Ljunggren-Rose et al. (1) present results from a study assessing the effect of anacardic acid, a salicylic acid derivative with a 15- or 17-carbon-containing alkyl chain substituent (i.e., 2-hydroxy 6-alkylbenzoic acid), on remyelination. Anacardic acids are phytochemicals that are found in foods such as cashews and mangoes. Myelin is the lipid-rich lamellar sheath that provides the electrical insulation around axons of nerve cells. Intact myelin is critical for axonal function because it enables efficient saltatory propagation of the action potential. In the central nervous system (CNS), myelin is formed and actively maintained by oligodendrocytes. Remyelination is the repair and formation of new myelin sheaths in areas where damage has occurred. Multiple sclerosis (MS), a chronic and disabling CNS disease characterized by blood–brain barrier breakdown, inflammation and lesion formation, demyelination, axonal injury, and neurodegeneration, is the most common disorder of myelin. Although several disease-modifying therapies, including oral medications, have become available for treating MS, all of the currently approved drugs are immunomodulatory agents that do not directly address the axonal injury and neurodegeneration that commences early in the course of the disease and contributes to disability and disease progression. There is an unmet need for neuroprotective and neuroreparative therapies for progressive MS. Myelin loss in MS can occur as a consequence of inflammatory attack on the myelin sheath, oligodendrocyte loss, and loss of trophic support from glia. When demyelination occurs, axons become vulnerable to neurodegeneration. Remyelination of MS lesions is variable but occurs as a result of net myelin production by oligodendrocyte precursor cells (OPC) that undergo proliferation and maturation with some contributions from the oligodendrocytes that have retained functional capacity to produce myelin. When lesions remyelinate, they can be seen as “shadow plaques” in magnetic resonance imaging, but the resultant degree of myelination is generally to levels that … [↵][1]1Email: murali{at}buffalo.edu. [1]: #xref-corresp-1-1