Anti-MAG peripheral neuropathy

Anti-MAG Peripheral Neuropathy is a specific type of peripheral neuropathy in which the person’s own immune system attacks cells that are specific in maintaining a healthy nervous system. As these cells are destroyed by antibodies, the nerve cells in the surrounding region begin to lose function and create many problems in both sensory and motor function. Specifically, antibodies against myelin-associated glycoprotein (MAG) damage Schwann cells. While the disorder occurs in only 10% of those afflicted with peripheral neuropathy, people afflicted have symptoms such as muscle weakness, sensory problems, and other motor deficits usually starting in the form of a tremor of the hands or trouble walking. There are, however, multiple treatments that range from simple exercises in order to build strength to targeted drug treatments that have been shown to improve function in people with this type of peripheral neuropathy. Anti-MAG Peripheral Neuropathy is a specific type of peripheral neuropathy in which the person’s own immune system attacks cells that are specific in maintaining a healthy nervous system. As these cells are destroyed by antibodies, the nerve cells in the surrounding region begin to lose function and create many problems in both sensory and motor function. Specifically, antibodies against myelin-associated glycoprotein (MAG) damage Schwann cells. While the disorder occurs in only 10% of those afflicted with peripheral neuropathy, people afflicted have symptoms such as muscle weakness, sensory problems, and other motor deficits usually starting in the form of a tremor of the hands or trouble walking. There are, however, multiple treatments that range from simple exercises in order to build strength to targeted drug treatments that have been shown to improve function in people with this type of peripheral neuropathy. Myelin is an important part of neuron cells and provides insulation allowing the neuron’s action potential to travel faster and more consistently. In order to provide insulation, multiple layers of closely opposing membrane are wrapped around the axon. By acting as an electrical insulator, the conduction ability of the axon is sped up considerably allowing action potentials to travel at a much faster rate, about fifteen times faster in certain cases. This ability allows the nervous system to send messages faster and more accurately. Disruption of the myelin sheath on cells that are normally myelinated allows leakage of action potential much like a faulty wire will allow leakage of electricity in a circuit. This slows the messages being sent along those nerves and disrupts normal function. Schwann cells are the cells in the peripheral nervous system that create and maintain myelin sheaths on neurons. These are the glial cells of the peripheral nervous system and are located around the axons that they serve. Damage to these cells result in degeneration of the myelin sheath and inevitably lead to problems in communication for the nervous system. Myelin-associated glycoprotein (MAG) is a glycoprotein that is specific to Schwann cells, which create myelin for nerve cells in the peripheral nervous system. Research through cloning of the rat MAG gene has shown that it is a type I transmembrane protein meaning that it contains domains both inside the cell membrane and outside the cell membrane. Expression of this glycoprotein is very specific to myelin-forming cells and begins very early in the myelination process in order to function in the early development of axons in the central nervous system. The expression continues to be relatively high even in mature animals, however, suggesting that it is associated with not only formation but maintenance as well. Research through knockout mice, or mice with the MAG gene removed, has shown that this glycoprotein serves heavily in the formation of myelin but also show that early development of the peripheral nervous system is relatively normal even without the presence of MAG. The knockout mice generally show many motor deficits, however, as they age caused by the degeneration of the myelinated axons further suggesting the need for these glycoproteins in maintenance of the sheaths. While it is still unclear as to the exact mechanism or pathway by which MAG affects myelination, studies suggest that MAG serves in a receptor role to begin a signaling cascade begun by activation from an external source. MAG has also been shown to bind as a ligand to a receptor on the axonal surface which suggests that the external stimulus activating the creation of myelin comes from the nerve cell or cells that these glycoproteins are bound to. Antibodies are created by the body that can then attack and disrupt the function of myelin associated glycoproteins. These antibodies have been found to bind to the external domain of the glycoproteins and inhibit any other signaling to occur. As these proteins are important in various signal cascades that eventually lead to the Schwann cells creating myelin, these antibodies basically halt myelin creation leading to the neuropathy. There is still, however, much debate as to the actual cause for these antibodies to be created. There has been some research to suggest that these antibodies are linked to various forms of amyloidosis as patients with amyloidosis experience elevated anti-MAG antibodies usually leading to a form of neuropathy. This does not, however, provide any evidence as to the mechanisms behind the creation of the antibodies. People with this disease have shown many sensory and muscular symptoms. Most patients have a sensory ataxia, or sensory loss in various extremities, along with mild to moderate muscle weakness, usually starting in the toes and fingers and moving inward. Most patients also present a mild to moderate tremor in the extremities which increases as the disease progresses. More severe symptoms occur after the disease progresses and there is much more damage to the myelin sheaths in the peripheral nervous system. These can present as debilitating tremors that prevent patients from doing normal tasks, complete sensory loss on limbs, and, in some cases, extensive muscle atrophy.