Multiple Sclerosis: Re-expression of a developmental pathway
Multiple sclerosis (MS) is an autoimmune disease that affects a part of the body known as the central nervous system or CNS. The CNS consists mainly of the brain and spinal cord. Surrounding and protecting the CNS nerve fibers is a tissue known as myelin, which protects and quickens the nerve impulses sent along those fibers. This myelin is created by glial cells known as oligodendrocytes which reside on the axon itself. In MS, the nerve fibers demyelinate, causing a scar tissue known as sclerosis to form in areas that a called plaques or lesions. The symptoms of this disease are varied and include vertigo and dizziness, cognitive problems, emotional instability, fatigue, numbness, spasticity, vision problems, and many more. As the authors point out, there are well documented cases of remyelination of the CNS in MS patients, but unfortunately it is not well understood. This article seeks to explain how remyelination of the CNS is prohibited in this disease by the re-expression of a pathway that is normally only used in the human body very early in development. During mammalian CNS development, a receptor on oligodendrocyte precursors known as Notch1 are contact mediated into activation by the ligand Jagged1. Jagged1 is
Hes5 was also detected in the same population of oligodendrocytes. The cells grown with Jagged1 showed fewer processes than those grown without. They were then compared with standard astrocytes and showed that the gene expression profile of the treated astrocytes were markedly changed, proving biological significance of the cytokines. However, it appears that in some cases this pathway is re-activated later in life, causing MS. The final test was the effect of Jagged1 signaling on differentiation and maturation of in vitro oligodendrocytes. The northern blotting (using probe Genbank R70685) showed that the astrocyte cultures induced Jagged1 mRNA within three hours of treatment with TGF-beta1. The goal of this is to allow them to move to other parts of the body before they develop and become stationary. Blocking its actions once it is released may stop or even reverse the effects of the disease, but it will most likely lead to dependency on drug or gene therapy for the rest of the patient's life. Also, actively demyelinating and remyelinating tissues were checked for Jagged1 together, and while it did appear in the demyelinating, it was not present in the remyelinating samples. The research seeks to discover if the Jagged1 ligand can be blocked, allowing the remyelination of the axons. It happened to strongly modulate Jagged1 along with other changes leading to the restructuring of the extracelluar matrix. They add that in order to gain control over the disease, the cure must start at the source; understanding what causes the disease to begin. The most obvious conclusion one could draw is that the inflammatory compound TGF-beta1 is the trickle from the brain that begins the cascade of this disease. These results were very reproducible and suggest that Jagged1 inhibits oligodendrocyte maturation in mammalian central nervous system. The first goat was to prove that the Notch1 pathway was upregulated and expressed in MS patients.
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