Build muscles and protect myelin

Abstract

Multiple sclerosis (MS) is a chronic and debilitating autoimmune disease of the central nervous system (CNS) in which a CNS-driven immune response destroys myelin, leading to wide range of symptoms including numbness and tingling, vision problems, mobility impairment, etc. Oligodendrocytes are the myelinating cells in the CNS, which are generated from oligodendroglial progenitor cells (OPCs) via differentiation. However, for multiple reasons, OPCs fail to differentiate to oligodendrocytes in MS and as a result, stimulating the differentiation of OPCs to oligodendrocytes is considered beneficial for MS. The β-hydroxy β-methylbutyrate (HMB) is a widely-used muscle-building supplement in human and recently it has been shown that low-dose HMB is capable of stimulating the differentiation of cultured OPCs to oligodendrocytes for remyelination. Moreover, other causes of autoimmune demyelination are the decrease and/or suppression of Foxp3-expressing anti-autoimmune regulatory T cells (Tregs) and upregulation of autoimmune T-helper 1(Th1) and Th17 cells. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS in which the autoimmune demyelination is nicely visible. It has been reported that in EAE mice, oral HMB upregulates Tregs and decreases Th1 and Th17 responses, leading to remyelination in the CNS. Here, we analyze these newly-described features of HMB, highlighting the putative promyelinating nature of this supplement.

Keywords: HMB; multiple sclerosis; myelin; oligodendrocyte.

Figure 1:

Maturation of OPC to OL by HMB. HMB stimulates the translocation of PPARα from cytoplasm to nucleus, which then binds to PPRE present in the promoter of myelin-specific genes. CBP and RNA polymerase also bind to PPRE to drive the transcription of myelin-specific proteins, ultimately leading to the maturation to OL.

Figure 2:

Schematic presentation of remyelination by body-building supplement HMB. While HMB and exercise help in body building, it also leads to the maturation of OPC to OL in the CNS, resulting in remyelination.