What makes myelin in pns

Morphological studies have provided us with information concerning the timing of myelination, the mechanism by which immature Schwann cells differentiate into a myelinating phenotype and lay down the myelin sheath around the axon, and the accumulation and the structure of the myelin membrane.

The last 20 years have seen the identification and the cDNA and gene cloning of the major PNS myelin proteins, which signalled the beginning of the knock-out decade: transgenic null-mutant mice have been created for almost every protein gene. The study of these animals shows that the formation of myelin is considerably less sensitive to molecular alterations than the maintenance of myelin.

This approach focuses on 1 repairing the damage that has already occurred and 2 preventing further injury to nerves and axons.

Several drugs that are currently approved for treating MS follow the second strategy. They work by suppressing or changing the activity of the immune system, protecting myelin from unwarranted attacks. However, to date none of the available medications address regeneration of lost myelin. Stem cell therapy is one avenue being explored in the search for treatments for MS.

These new stem cells were then infused into the spinal cords of mice models of MS where they secreted factors that helped the myelin-producing cells survive. Consequently, these mice had more myelination and less axonal damage compared to mice that did not receive stem cell infusions. While the results are promising, much more work will need to be done in human clinical trials to determine the therapeutic efficacy.

Continued research efforts funded by public and private institutions worldwide seek to understand how myelin is compromised in diseases like MS, revealing new possibilities for treatment and offering hope to the millions of people affected by these diseases. Her translational research focuses on molecular mechanisms of Alzheimer's disease and psychosis.

In addition to contributing to BrainFacts. Ask a neuroscientist your questions about the brain. Submit a Question. See how discoveries in the lab have improved human health. Read More. Personalize your monthly updates from BrainFacts. Sign Up. For Educators Log in. Research and Discoveries. Myelin is a fatty material that wraps around nerve cell projections.

In this image, myelin can be seen on either end of the nerve fibers. The gaps in the middle of the fibers are called nodes, which help transmit electrical signals in neurons. Desmazieres, et al. Journal of Neuroscience, In this illustration of a neuron, myelin is shown in yellow. This mode of travel by the action potential is called "saltatory conduction" and allows for rapid impulse propagation Figure 1A.

Following demyelination, a demyelinated axon has two possible fates. The normal response to demyelination, at least in most experimental models, is spontaneous remyelination involving the generation of new oligodendrocytes. In some circumstances, remyelination fails, leaving the axons and even the entire neuron vulnerable to degeneration.

Remyelination in the CNS: from biology to therapy. Nature Reviews Neuroscience 9, — All rights reserved. Figure Detail What happens if myelin is damaged? The importance of myelin is underscored by the presence of various diseases in which the primary problem is defective myelination. Demyelination is the condition in which preexisting myelin sheaths are damaged and subsequently lost, and it is one of the leading causes of neurological disease Figure 2.

Primary demyelination can be induced by several mechanisms, including inflammatory or metabolic causes. Myelin defects also occur by genetic abnormalities that affect glial cells. Regardless of its cause, myelin loss causes remarkable nerve dysfunction because nerve conduction can be slowed or blocked, resulting in the damaged information networks between the brain and the body or within the brain itself Figure 3.

Following demyelination, the naked axon can be re-covered by new myelin. This process is called remyelination and is associated with functional recovery Franklin and ffrench-Constant The myelin sheaths generated during remyelination are typically thinner and shorter than those generated during developmental myelination.

In some circumstances, however, remyelination fails, leaving axons and even the entire neuron vulnerable to degeneration. Thus, patients with demyelinating diseases suffer from various neurological symptoms. The representative demyelinating disease , and perhaps the most well known, is multiple sclerosis MS. This autoimmune neurological disorder is caused by the spreading of demyelinating CNS lesions in the entire brain and over time Siffrin et al.

Patients with MS develop various symptoms, including visual loss, cognitive dysfunction, motor weakness, and pain. Approximately 80 percent of patients experience relapse and remitting episodes of neurologic deficits in the early phase of the disease relapse-remitting MS. There are no clinical deteriorations between two episodes. Approximately ten years after disease onset, about one-half of MS patients suffer from progressive neurological deterioration secondary progressive MS.

About 10—15 percent of patients never experience relapsing-remitting episodes; their neurological status deteriorates continuously without any improvement primary progressive MS. Importantly, the loss of axons and their neurons is a major factor determining long-term disability in patients, although the primary cause of the disease is demyelination. Several immunodulative therapies are in use to prevent new attacks; however, there is no known cure for MS. Figure 3 Despite the severe outcome and considerable effect of demyelinating diseases on patients' lives and society, little is known about the mechanism by which myelin is disrupted, how axons degenerate after demyelination, or how remyelination can be facilitated.

To establish new treatments for demyelinating diseases, a better understanding of myelin biology and pathology is absolutely required. How do we structure a research effort to elucidate the mechanisms involved in developmental myelination and demyelinating diseases?

We need to develop useful models to test drugs or to modify molecular expression in glial cells. One strong strategy is to use a culture system. Coculture of dorsal root ganglion neurons and Schwann cells can promote efficient myelin formation in vitro Figure 1E. Researchers can modify the molecular expression in Schwann cells, neurons, or both by various methods, including drugs, enzymes, and introducing genes , and can observe the consequences in the culture dish. Modeling demyelinating disease in laboratory animals is commonly accomplished by treatment with toxins injurious to glial cells such as lysolecithin or cuprizone.

Autoimmune diseases such as MS or autoimmune neuropathies can be reproduced by sensitizing animals with myelin proteins or lipids Figure 3. Some mutant animals with defects in myelin proteins and lipids have been discovered or generated, providing useful disease models for hereditary demyelinating disorders. Further research is required to understand myelin biology and pathology in detail and to establish new treatment strategies for demyelinating neurological disorders.

Myelin can greatly increase the speed of electrical impulses in neurons because it insulates the axon and assembles voltage-gated sodium channel clusters at discrete nodes along its length. Myelin damage causes several neurological diseases, such as multiple sclerosis. Future studies for myelin biology and pathology will provide important clues for establishing new treatments for demyelinating diseases. Brinkmann, B. Neuron 59 , — Franklin, R. Remyelination in the CNS: From biology to therapy.

Contact Us. Start Here. Stem cell therapies show early successes in lab models. Here are a few related topics that may interest you. Our MS Navigators help identify solutions and provide access to the resources you are looking for.

Call or contact us online.