Bose Ahana, Pahan Kalipada
Division of Research and Development, Jesse Brown Veterans Affairs Medical Center, Chicago, IL, USA.
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
NeuroImmune Pharm Ther. 2024 Oct 16;3(3-4):175-182. doi: 10.1515/nipt-2024-0015. eCollection 2024 Sep.
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.
多发性硬化症(MS)是一种慢性且使人衰弱的中枢神经系统(CNS)自身免疫性疾病,在该疾病中,由CNS驱动的免疫反应会破坏髓鞘,导致包括麻木、刺痛、视力问题、行动障碍等多种症状。少突胶质细胞是中枢神经系统中的髓鞘形成细胞,它们由少突胶质前体细胞(OPCs)通过分化产生。然而,由于多种原因,在MS中OPCs无法分化为少突胶质细胞,因此,刺激OPCs分化为少突胶质细胞被认为对MS有益。β-羟基-β-甲基丁酸酯(HMB)是一种在人类中广泛使用的增肌补充剂,最近有研究表明,低剂量的HMB能够刺激培养的OPCs分化为少突胶质细胞以进行髓鞘再生。此外,自身免疫性脱髓鞘的其他原因是表达Foxp3的抗自身免疫调节性T细胞(Tregs)减少和/或受到抑制,以及自身免疫性辅助性T细胞1(Th1)和Th17细胞上调。实验性自身免疫性脑脊髓炎(EAE)是MS的一种动物模型,其中自身免疫性脱髓鞘现象清晰可见。据报道,在EAE小鼠中,口服HMB可上调Tregs并降低Th1和Th17反应,从而导致中枢神经系统的髓鞘再生。在此,我们分析了HMB这些新描述的特征,强调了这种补充剂假定的促髓鞘形成特性。