Acid Sphingomyelinase: Multiple Sclerosis

ACID SPHINGOMYELINASE: MULTIPLE SCLEROSIS Your Name Subject and Section Date Introduction to Multiple Sclerosis Multiple sclerosis (MS) is a chronic degenerative disease that induces a demyelinating reaction to the central nervous system (CNS) and, also, the most common cause of permanent neurological disability in young adults (Nakahara, Maeda, Aiso, and Suzuki, 2012); however, the exact causes of this disease is unknown (Dasgupta & Ray, 2017; Nakahara, Maeda, Aiso, and Suzuki, 2012). In vertebrates, most axons are evolutionary specialized with a spirally wrapped layer of myelin sheath. The myelin sheath facilitates the rapid exchange of nerve cell's electrical impulses. Additionally, the myelin sheath is produced by the Schwann cells in the peripheral nervous systems and by the oligodendrocytes in the CNS (Jana & Pahan, 2010). The distinctive pathological attribute of the disease is an autoaggressive immune reaction with inflammatory infiltration of the CNS that causes degradation reactions on the myelin sheath leading to neurological disorders (Becker, et al., 2017). These neurological disorders, due to the degradation of the myelin sheath, commonly include the symptomatic impairment of the motor, sensory, visual and autonomic bodily functions of a person (Compston & Coles, 2008). Specifically, T cells migrate across the blood brain barrier (BBB) and be activated to become myelin-specific T cells (See figure 1) (Halmer, Walter, & Faßbender, 2014). When myelin-specific T cells got activated, it signals the BBB into letting other T cells cross the barrier (Jane & Pahan, 2010). Additionally, the myelin activated T cells secrete pro-inflammatory cytokines, including  tumor necrosis factor-alpha (TNFα), interferon-gamma (IFNγ), transforming growth factor-beta (TGF-β) and interleukin-6 (IL-6) (Dasgupta & Ray, 2017), that triggers the sphingomyelin pathway and also stimulate the microglia, macrophages, astrocytes and recruit B cells (Jane & Pahan, 2010). In the case of MS patients, the additional substances, due to the increased myelin-specific T cells and increased cytokine production, targets both the myelin and the oligodendrocytes that produce the myelin sheath in the CNS (see figure 2) (Jana & Pahan, 2010); however, the rate of demyelination due to the loss of the oligodendrocyte as a major contributor to stimulate myelin degradation is unclear (Caprariello, Mangla, Miller, & 114304789805Figure 1. The diagram shows the crossing of T cells and other cells through the BBB. Also, the diagram shows different pathways and cytokines that contributes to the loss of myelin sheath of the neuron. From Jana, A. & Pahan, K. (2010). Sphingolipids in multiple sclerosis. Neuromolecular Medicine, 12(4), 351-361. doi: 10.1007/s12017-010-8128-400Figure 1. The diagram shows the crossing of T cells and other cells through the BBB. Also, the diagram shows different pathways and cytokines that contributes to the loss of myelin sheath of the neuron. From Jana, A. & Pahan, K. (2010). Sphingolipids in multiple sclerosis. Neuromolecular Medicine, 12(4), 351-361. doi: 10.1007/s12017-010-8128-4271145142512100Selkirk, 2012). Demyelination can occur on varying mechanisms depending on the condition of the MS patients, where the disease's expression is stimulated by different factors such as proteolytic enzymes, cytokines, oxidative products, and free radicals (Dasgupta & Ray, 2017). According to the studies made by Dasgupta and Ray (2017), sphingolipids are hypothesized to be metabolically altered in MS that may cause an untimely cell death of oligodendrocytes and neurons. 1172020-561600 6350382270Figure 2. Oligodendrocytes support axons. A. Its shows the role of oligodendrocyte in the production of myelin (green) that covers the axons of the neuron. B. It shows the loss of oligodendrocyte and the gradual degradation of the myelin sheath. From Stassart, R.M., Mobius, W., Nave, K., and Edgar, J.M. (2018). The Axon-Myelin Unit in Development and Degenerative Disease, Frontiers in Neuroscience, 12, 1-22. doi: 10.3389/fnins.2018.0046700Figure 2. Oligodendrocytes support axons. A. Its shows the role of oligodendrocyte in the production of myelin (green) that covers the axons of the neuron. B. It shows the loss of oligodendrocyte and the gradual degradation of the myelin sheath. From Stassart, R.M., Mobius, W., Nave, K., and Edgar, J.M. (2018). The Axon-Myelin Unit in Development and Degenerative Disease, Frontiers in Neuroscience, 12, 1-22. doi: 10.3389/fnins.2018.00467 Additionally, the information gathered in the cerebrospinal fluid (CSF) shows high levels of catabolic products from the sphingomyelin pathway, including the hydrolysis of sphingomyelins by enzymes sphingomyelinases, reveals conditions about the alterations regarding the CNS that leads to axonal damage and untimely cell death (Pieragostino, et al., 2018). Although the precise cause of MS is still not known (Dasgupta & Ray, 2017; Nakahara, Maeda, Aiso, and Suzuki, 2012), the role of sphingomyelins and the enzyme acid sphingomyelinase in the development of multiple sclerosis should be further studied since both are involved in producing catabolic products that may cause the unt...