Multiple Sclerosis: Re-expression of a developmental pathway

A detailed Summary of 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

The first goat was to prove that the Notch1 pathway was upregulated and expressed in MS patients. The researchers did a cDNA microarray screen in which astrocyte cultures were treated with cytokines TGF-beta1, interleukin-1 (IL-1), and interferon-v (IFN-v). 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. TGF-beta1 was the only cytokine to show changes in the gene expression profile of the astrocytes consistent with what the researchers were looking for. It happened to strongly modulate Jagged1 along with other changes leading to the restructuring of the extracelluar matrix. These findings were then further checked with northern and western blotting and confocal microscopy. The northern blotting (using probe Genbank R70685) showed that the astrocyte cultures induced Jagged1 mRNA within three hours of treatment with TGF-beta1. Western blotting with a specific antibody gave a strong induction of the Jagged1 protein within six hours. Combined, this data showed that the Notch1 pathway was re-expressed and activated in the inflamed CNS.

The researchers then tested to see if these results in vitro would be the same in actual tissue. The lesions used all showe

Some common words found in the essay are:
TGF-beta1 Hes5, Jagged1 Notch1, CNS CNS, TGF-beta1 Western, CNS MS, TGF-beta1 Blocking, Notch1 Hes5, , Jagged1 Jagged1, Genbank R70685, expression profile, gene expression profile, nerve fibers, gene expression, mature humans, cytokines tgf-beta1, demyelinating remyelinating, remyelination cns, central nervous, nervous system, ms patients, central nervous system,

Approximate Word count = 885
Approximate Pages = 4 (250 words per page double spaced)

Category: Science