What Is Myelin Gene Regulatory Factor ( MRF )?

Multiple sclerosis (MS) is an unpredictable, immune mediated disease of the central nervous system (CNS) (Definition of MS). This disease is estimated to affect more than 400,000 people in the United States alone, and about 2.5 million worldwide. In the United States, about 200 new cases of MS are discovered weekly (Pietrangelo, Anne and Higuera, Valencia) . In a healthy person, an insulation covering called myelin, coats the nerve fibers in the CNS (Article from mom). When one develops MS, the communication between their brain and other parts of his/her body is disrupted as “an abnormal immune-mediated response” attacks the myelin coating that encloses nerve fibers in the CNS. This causes a disturbance in communication between the CNS and

The breakdown of the myelin sheath is caused from a mutation of the gene that makes the Adrenoleukodystrophy protein (ALDP). This ALD protein helps the body metabolize saturated very-long-chain fatty acids found in the serum and tissues of the central nervous system. The newly mutated gene no longer acts as a help aid to breaking down the long-chain fats. Therefore, the body starts accumulating an abnormal amount of fat in the nervous system, adrenal gland and testes that sets off an unusual response in the immune system; demyelination.

Myelin, the common factor in each disease, is a subsatnce that surrounds and insulates axons on some nerve cells, allowing for a faster transporting of signals and proper functioning of the nervous system. A demyelinating disease results in the damage of nerve fibers in the brain and spinal cord due to the myelin sheath being destroyed, which is life threatening.

By attacking the myelin MS causes inflammation and damage to the myelin itself (MS Society of Canada, 2016). Myelin is the main source of transportation for nerve impulses; this is done through the nerve fibres that are protected by the myelin (MS Society of Canada, 2016). If the myelin is only slightly damaged the nerve impulses can continue with a few minor interruptions, but if the damage is extensive then problems become more apparent (MS Society of Canada, 2016).

Multiple Sclerosis is an inflammatory demyelinating neurodegenerative disorder of the central nervous system that has the potential to cause significant disability in those affected through the body's immune system attacking and destroying the myelin sheaths surrounding the axons. Myelin is rich in lipids and proteins that form layers around the nerve fibers and acts as insulation and protection. This damage to the myelin in the CNS, and to the actual nerve fibers, has the potential to block the transmission of nerve signals between the brain and spinal cord and also other parts of the body. This disruption of the nerve signals produces the primary symptoms of MS which then possibly lead to secondary and tertiary symptoms stemming from these

Even though, we understand that T-cells have gone rogue and cause the damage to the myelin no one understands why the T-cells start to attack the myelin to begin with. However, there is interesting data that suggest that genetics, a person's environment, and possibly even a virus may play a role”(WebMD). These theories have yet to be proven and subsequently prevents a cure.

Through inflammation and destruction of the myelin sheath covering nerves, irreversible damage slows, redirects, or stops nerve impulses. This is due to the fact that nervous tissue cannot repair itself resulting in plaques also referred to as MS lesions being left behind. Demyelination can occur in grey or white matter of the nervous system with wide reaching affects due to the immune system attacking the nervous system systemically as opposed to being confined to a small area. Huether, S and McCance, K (2012) found that MS is usually triggered in genetically predisposed individuals by a viral infection, traumatic injury, or

Researchers discovered that when oligodendrocytes in healthy individuals are damaged, the brain can produce new cells to repair the damaged ones. However, people with MS have trouble making new oligodendrocytes. Therefore, once an immune attack occurs, the brain is unable to provide a way to resolve the damages. One drug, called Guanabenz, kept oligodendrocytes alive, easing MS symptoms and slowing its progression. While still in trial phases, Guanabenz and other potential drugs may be successful treatments to MS in the future. Ongoing experiments are also taking place in the gut, where the immune system is exposed to environmental factors. Nevertheless, scientists are uncovering new information about multiple sclerosis each and every

Two other characteristics are involved in the disease process: inflammation and the formation of lesions or plaques in the central nervous system – or CNS (Mayo Clinic Staff, 2014). Lesions are formed when oligodendrocytes – myelin-building cells – are lost causing the myelin sheath to thin or even completely breakdown leaving the nerve axon exposed and unable to send effective signals to your muscles (Huether and McCance, 2008). The oligodendrocytes attempt to remyelinate the axons but with multiple attacks, the

When the nerves of the body become damaged and no longer has the myelin sheath to protect them, then the damage causes the brain to fail to correctly transmit signals throughout the body. This causes the nerves to function irregularly which leads to problems with vision, balance, muscle control, and other basic body functions. Furthermore these problems can cause paralysis, fatigue, muscle weakness or muscle spasms, blurred vision or double vision, numbness and tingling, sexual problems, poor bladder or bowel control, pain,depression, problems focusing or remembering, and tremors.

Alexander Disease is a rare defect involving the nervous system. It is part of a classification of uncommon genetic disorders called leukodystrophies that affect the central nervous system by interfering with the growth and nourishment of the myelin sheath. Myelin sheath shields nerve fibers and promotes rapid transmission of nerve impulses. If myelin is not properly nurtured, the transmission of nerve impulses can become disrupted causing serious impairment of nervous system functions. Although a majority of cases with early onset exhibit a distinct deficiency in the formation of myelin, white matter defects are sometimes not detected in cases accompanying later onset. Contrary to its classification, the universal characteristic among all Alexander disease cases is actually the presence of atypical protein compounds called Rosenthal fibers. They present themselves in a particular type of glial cell found in the central nervous system known as an astrocyte. Glial cells provide nutrients for neurons, absorb dead neurons, and physically reinforce their structure. Rosenthal fibers are composed of substantial quantities of glial fibrillary acidic proteins (GFAP). GFAP is known to sustain the mechanical strength of astrocytes, but in this case it is a defect in GFAP that has been found to interfere with the function of astrocytes and ultimately causes the leukodystrophy. When tested on mice, the mutation of GFAP caused a new, toxic effect, rather

Stem cells are located in the spinal cord and they are hard to identify (Konstantinos et al., 2008). Human embryonic stem cells have advantages that other cell types do not contain. They have a large capacity for differentiation and for expansion. They also help in remyelination. However, studies have shown that human embryonic stem cell derived oligodendrocyte progenitor cells can help in neuroprotection, homeostatic maintenance, suppressing inflammation, and promoting the regeneration of axons. (Sharp et al., 2010). Most of the neural stem cell potential is in ependymal cells (Meletis et al., 2008). Transplanting these oligodendrocyte progenitor cells just one week after the injury showed widespread oligodendrocyte remyelination throughout the white matter (Keirstead et al., 2005).

Multiple Sclerosis is a disabling disease of the brain and spinal cord. The article stated, “ Adult OPCs retain the capacity to differentiate into myelinating oligodendrocytes in response to injury or demyelinating diseases, such as

Researchers used BrdU pulsing to identify the target cells they wanted to monitor for possible growth and change. In order to evaluate the effects of aspirin on oligodendroglia in vitro, multiple aspects were studied. Cultures of neural stem cells and OPC’s were taken, incubated, stained, and treated with varying doses of aspirin. Cells are analyzed under the electron microscope to see the effects aspirin may have on oligodendrocyte lineage and development, as well as OPC proliferation and differentiation. Specific stains are used as markers for the cells being targeted as well as the processes they may be undergoing, such as proliferation.

Understanding how neuronal injury and disease differentially determine glia responses may have major implications for disease progression, outcome of a given therapy, the identification of novel therapeutic targets and development of regenerative therapies in the future. Here, we provide evidences suggesting that the