Multiple System Atrophy : An Adult Onset Progressive Neurodegenerative Disease

Multiple sclerosis (MS) involves an autoimmune process that develops when a previous viral insult to the nervous system has occurred in a genetically susceptible individual. B lymphocytes, plasma cells, and activated T cells, along with proinflammatory cytokines, cause inflammation, oligodendrocyte injury and demyelination. Early inflammation and demyelination lead to irreversible axonal

Multiple Sclerosis (MS) is a neurologic disease that affects the Central Nervous System (CNS) through cellular immune response and the demyelination of CNS white matter (McCance et al., 2014, pp. 630–633). The initial causes of MS are unknown however, it is believed that it could possibly be due to an immune response to an initiating infection or an autoimmune response to CNS antigens on the myelin itself (Brück, 2005) (Miljković and Spasojević, 2013). MS is a result of the degradation of the myelin sheath surrounding neurons and therefore disrupts the transmission of action potentials along these cells. MS can display itself in the form of symptoms ranging from muscle weakness to trouble with sensation and coordination (NHS, 2016). The degradation of myelin leads the body to attempt to remyelinate the neurons, a process that in turn leads to the thickening of the cell by glial cells and this causes lesions to form (Chari, 2007). It is this thickening (sclerae) from which the disease gets its name. Sufferers of MS can either have a relapsing type of MS, in which there are episodes that lead to the worsening of symptoms for a period of time, or a progressive type of MS where symptoms gradually progress and worsen (McCance et al., 2014, pp. 630–633).

The central nervous system (CNS) comprises grey matter, which contains neuron cell bodies and white matter, which contains the nerve axons. Most of the nerve axons are concentrically wrapped around by lipid-rich biological membrane, known as the myelin sheath. In the CNS, myelin is produced by oligodendrocyte. a type of glial cell. (Pfeiffer et al., 1993). These electrical insulating, multilamellar membranes significantly increase the electrical resistance, in which to prevent leakage of electrical currents from the axons, as well as decrease electrical capacitance to reduce the ability of the axons to store electrical energy (Shivane &

Multiple sclerosis is characterized by inflammation, demyelination, and axonal damage in the brain and spinal cord with a loss of myelin that covers the axons. As the myelin sheath regenerates, scar tissue forms, which looks like plaques on magnetic resonance imaging scans. Multiple sclerosis arises when immune-mediated inflammation activates T cells and causes the T cells and immune mediators to cross the blood-brain barriers into the CNS and attack oligodendrocytes (ie, a type of neuroglial cell with dendritic projections that coil around axons of neural cells). When the oligodendrocytes are attacked, the myelin sheath is replaced by scar tissue, which forms throughout the CNS. As a result of damage to the myelin sheath, the ability to transmit and conduct nerve impulses along the spinal cord and in the brain is interrupted, leading to muscle weakness, fatigue, loss of coordination, balance impairment, and cognitive and visual disturbance (DeLuca & Nocentini, 2011). This disease is characterized by unpredictable remissions that occur over several years. During periods of remission, the myelin sheath usually regenerates and symptoms may resolve, but the myelin cannot be completely repaired. As the disease progresses, the myelin sheath is destroyed and nerve impulses become much slower or absent and symptoms worsen. When degeneration exceeds self-repair ability, permanent disability results. There are four defined clinical types of

Multiple Sclerosis, commonly known as MS is an autoimmune disease of the central nervous system. Scientists have been studying MS since the 19th century. In MS, the body’s immune system produces cells and antibodies that attack myelin in your brain which is essential for the nerves in your brain and spinal cord to conduct electricity to perform its function. The attack on myelin results in vison loss, paralysis, numbness, muscle weakness, difficulty walking, stiffness, spasms, and bladder and bowel problems. MS has varying degrees of severity and affects people between the ages of 20-50, mostly women. Although there are treatments, there is no cause and cure yet.

Multiple sclerosis is an unpredictable, crippling neurological disease of the central nervous system, which affects the flow of information within the brain, and between the brain and body. The name is this disease refers to multiple areas of scarring throughout the brain and spinal cord. This scarring is a result of what happens when the body attacks itself. A substance called Myelin surrounds the nerves to help protect them (Healthline.com, 2015). Multiple Sclerosis is thought to occur in a genetically susceptible individual (although there is no evidence to show that the disease is directly inherited) influenced one or more environmental factors. MS is thought to be an autoimmune disease, however others disagree as the target of the immune

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

2010). The neuroinflammation is an early, non-specific immune reaction to tissue damage or pathogen invasion (Lee et al. 2010). Inflammation of the central nervous system (CNS) is characterized by increased glial activation, pro-inflammatory cytokine concentration, blood-brain-barrier permeability, and leukocyte invasion (Lee et al. 2010). Microglia are cells that support and protect neuronal functions (Lee at al. 2010). They act as the first and main form of active immune defense that orchestrate the endogenous immune response of the Central Nervous System. The microglia play a central role in the cellular response to pathological lesions such as Aβ. Aβ can attract and activate microglia, leading to clustering of microglia around Aβ deposits sites in the brain (Lee et al. 2010). Even though microglia have neuroprotective functions, neurotoxic mechanisms which involves continuous activation of microglia and toxic factors are released by microglia, which may lead to neuroinflammation (Lee et al. 2010). Astrocytes (star-shaped glial cells) are the most abundant cells in the brain and are located in the brain and spinal. Astrocytes have various functions such as: biochemical support of endothelial cells of the BBB, supplying nutrients to the nervous tissue, maintenance of extracellular ion balance, and healing the brain and spinal cord following traumatic injury (Lee et al., 2010). Chemokines are released by astrocytes which attract microglia and they further express proinflammatory products, thus increasing neuronal damage in the pathogenesis of AD (Lee et al., 2010). Astrocytes play a critical role in Aß clearance and degradation, and they also provide trophic support to neurons forming a protective barrier between Aß deposits and neurons (Wyss-Coray et al., 2003). Neurons contribute to the production of

Multiple sclerosis, or MS as it is more commonly referred, is an immune mediated disease that involves the body's own defense mechanism, specialized immune cells, that ultimately attacks the central nervous system. Specifically, the myelin protein that coats axons and forms an electrically insulating layer for quicker processing of the nervous system, is attacked by cytotoxic cells that have crossed into the CNS. In a healthy patient, the blood brain barrier cannot be crossed by cytotoxic cells and it is speculated that an environmental component or outside source mediates this crossing. When the myelin is attacked, it forms scars in the CNS, as multiple sclerosis literally translates to “many scars,” which is the direct result of the disease. The scars disrupt the normal nerve impulses that travel through the central nervous system, and can cause a variety of symptoms including loss of cognition, fatigue, or numbness in the body (Evidence).

MS is an autoimmune disease, meaning the immune system attacks the bodys own myelin sheath protection. The damaged myelin and axon fibers is caused by overactivated T cells.

Multiple sclerosis, also known as MS, is an autoimmune and inflammatory disease that is very painful for both the patient and care giver. In the disease, there is inflammation and neurodegeneration acting at the same time. There is currently no known primary cause of multiple sclerosis. The disease is however characterized by damaged fatty myelin sheaths around the axons of the brain and the spinal cord. Myelin is a mixture of proteins and phospholipids that protects many nerve fibers enabling speed at which impulses are conducted. It is pathologically characterized as the presence of glial scars all over in the central nervous system. The disease was discovered by the French neurologist Jean-Martin Charcot in 1868 when he examined the brain

Multiple sclerosis, commonly known as MS, is an auto-immune disease. An auto-immune disease is one in which the body attacks itself. In this particular disease, the central nervous system is being attacked. Specifically, the myelin sheath, or the fatty substance that coats and protects nerve fibers in the brain and spinal cord, is attacked. The attacks cause scar tissue, which makes it difficult for signals to travel between the brain and body. Eventually, the nerves may deteriorate, which is a process that is completely irreversible [5]. See the figure below for more detail.

Multiple Sclerosis is a chronic progressive disease involving damage to the myelin sheaths of nerve cells in the brain and spinal cord. The exact cause of multiple sclerosis is unknown but we know that something triggers the immune system to attack the central nervous system (CNS). MS happens when your immune system attacks a fatty material called myelin and without this outer shell, your nerves become damaged. The resulting damage to myelin that insulates wire like nerve fibers is a disruption of signals to and from the brain. This hiatus of communication signals causes unpredictable symptoms such as numbness, tingling, mood changes, memory problems, blindness, paralysis, fatigue and pain. People who have MS experience the disease differently,

Under normal condition tau binds to microtubules, stabilizing neuronal structure and integrity. Hyperphosphorylation of tau is assumed to be the cause of the formation of paired helical filaments - neurofibrillary tangles (NFT). The principle components of the senile plaques are neurofibrillary tangles in the cell bodies, neuropil threads, and neurites as well as extracellular A-beta amyloid. These lesions are surrounded by microglial and astrocytes. The brain regions affected by Alzheimer’s disease also contain neuritic or senile plaques in which extracellular deposits of amyloid are surrounded by dystrophic axons as well as the process of astrocytes and microglia. The principle constituent of amyloid is a 4kDa peptide called A-beta amyloid. A-beta amyloid is cleaved from a larger precursor protein called amyloid precursor protein. Similar abnormalities occur in transgenic mice with mutant APP and in individuals with Alzheimer’s

human MS. In this model, the injection of BM-MSCs improvedthe clinical course and promoted peripheral T cell tolerance tomyelin proteins, thus reducing the migration of pathogenic T cellsto the CNS (Morando et al., 2012; Bai et al., 2009; Gerdoni et al.,2007; Zhang et al., 2005). In this model setting, the therapeuticeffects of MSCs were not likely attributable to graft- or host-driven remyelination, but rather were mediated by an immunemodulatory mechanism guarding the CNS from immune-mediatedinsult (Morando et al., 2012; Rafei et al., 2009). Similarly, BM-MSCs have been reported to have been successfully used in animalmodels of acute disorders, such as stroke or spinal cord injury,while they are disappointingly unable to remedy the neurologicaldeficits when chronic neural damage occurs. These observationssuggest that the immunosuppressive nature of BM-MSCs, whichis substantially increased by inflammatory cues, allows them tomodulate immune response and inhibit inflammation (Uccelli et al.,2011).These findings pose the question of whether the reported ben-eficial effects of BM-MSCs in immune models such as EAE are dueto suppression of the peripheral immune response that damagesmyelin or due to immune-independent mechanisms of action, suchas the direct replacement of the dying cells, oligo/neuroprotection,and/or enhancing endogenous repair. This question is furtherhighlighted by a recent study conducted in a non-immune toxinmodel in which intravenously injected BM-MSCs did