Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multiple sclerosis: Cholesterol crystals prevent regeneration in the central nervous system

05.01.2018

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system, in which the immune cells attack the insulating myelin sheath surrounding nerve fibers. The regeneration of intact myelin sheathes is a necessary prerequisite for patients to recover from MS relapses. Nevertheless, the ability to regenerate myelin decreases with age. A team from Technical University of Munich has published an explanation in "Science": Fat derived from myelin, which is not carried away rapidly enough by phagocytes can trigger chronic inflammation that in turn impedes regeneration.

The myelin sheath plays a decisive role in the function of the central nervous system: it is a specialized membrane enriched in lipids, which insulates nerve fibers so that electrical signals can be passed on quickly and efficiently.


Together with his team Prof. Mikael Simons researches the formation and removal of the myelin sheathes which surround nerve fibers and which are destroyed in Multiple Sclerosis.

A. Eckert / TUM

In MS, there is a multifocal autoimmune attack against the myelin sheath in the central nervous system, which causes neurological deficits such as loss of motor function. Regeneration of myelin is possible, but in MS it is inadequate.

One of the reasons is presumably chronic inflammation occurring in the lesions. A team led by TUM Molecular Neurobiology professor Mikael Simons has now discovered that after the destruction of myelin crystalline cholesterol can trigger persistent inflammation which prevents regeneration, similar as in arteriosclerosis.

Dangerous crystals

"Myelin contains a very high amount of cholesterol," explains Prof. Simons. "When myelin is destroyed, the cholesterol released has to be removed from the tissue." This is performed by microglia and macrophages, also referred to as phagocytes. They take up the damaged myelin, digest it and transport the non-digestible remainder, such as cholesterol, out of the cell by transport molecules.

However, if too much cholesterol accumulates in the cell, cholesterol can forms needle-shaped crystals, which cause damage the cell. Using a mouse model, Simons and his team showed the devastating impact of the crystalline cholesterol: It activates the so-called inflammasome in phagocytes, which results in the release of inflammatory mediators, attracting even more immune cells. "Very similar problems occur in arteriosclerosis, however not in the brain tissue, but in blood vessels," says Simons.

How well the microglia and macrophages did their job was ultimately also dependent on the age of the animal: the older the animal, the less effective was the clearance of cholesterol and the stronger the chronic inflammations. "When we treated the animals with a medication that facilitates the transport of cholesterol out of the cells, inflammation decreased and myelin was regenerated," says Mikael Simons. Next he and his team want to investigate whether this mechanism can be used therapeutically to promote regeneration in MS.

Newly discovered cells indicate regeneration

A crucial prerequisite for the development of therapies that promote repair is a better understanding of myelin formation. In another study, recently published in the journal "Science Translational Medicine" and led by Prof. Simons and Prof. Christine Stadelmann of the University of Göttingen's Institute of Neuropathology, provides important new insights into this process. The scientists discovered a novel oligodendroglial cell type. Oligodendrocytes are specialized glial cells that are responsible for myelination in the central nervous system.

"We believe that the BCAS1-positive oligodendrocytes that we discovered represent an intermediate stage in the development of myelin-forming cells. In humans they can only be identified for a relatively short period of time, exactly then when myelin is actually being formed," says Mikael Simons. In the human brain, for example, they are found in newborns, which generate myelin at high rate. In adults, these cells disappear, but they can be re-formed when myelin has been damaged and needs to be regenerated.

"We hope that the BCAS1 positive cells will help us to identify new regenerative medicines," says Mikael Simons. We can now rapidly screen for drugs that promote the formation of these cells, he adds. Furthermore they could be used to get a better understanding of exactly when and how myelin is created during the course of a human life, he says.

The two research projects were launched in close partnership with scientists at the Max Planck Institute for Experimental Medicine in Göttingen. Prof. Simons is also a member of the Excellence Cluster SyNergy and holds a post at the German Center for Neurodegenerative Diseases (DZNE).

Publications:
L. Cantuti-Castelvetri, D. Fitzner, M. Bosch-Queralt, M.-T. Weil, M. Su, P. Sen, T. Ruhwedel, M. Mitkovski, G. Trendelenburg, D. Latjohan, W. Moebius, M. Simons: Defective cholesterol clearance limits remyelination in the aged central nervous system, Science (2018). DOI: 10.1126/science.aan4183

M. K. Fard, F. van der Meer, P. Sanchez, L. Cantuti-Castelvetri, S. Mandad, S. Jaekel, E. F. Fornasiero, S. Schmitt, M. Ehrlich, L. Starost, T. Kuhlmann, C. Sergiou, V.Schultz, C. Wrzos, W. Brueck, H. Urlaub, L. Dimou, C. Stadelmann, M. Simons: BCAS1 expression defines a population of early myelinating oligodendrocytes in multiple sclerosis lesions, Science Translational Medicine (2017). DOI: 10.1126/scitranslmed.aam7816

Contact:
Prof. Dr. Mikael Simons
Technical University of Munich (TUM)
Chair for Molecular Neurobiology
Tel: +49-(0)89 440046495
msimons@gwdg.de

Weitere Informationen:

http://www.neuroscience.med.tum.de/index.php?id=5 Website of the Chair

Dr. Ulrich Marsch | Technische Universität München
Further information:
http://www.tum.de

More articles from Health and Medicine:

nachricht Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University

nachricht Microgel powder fights infection and helps wounds heal
14.11.2018 | Michigan Technological University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

Im Focus: Research icebreaker Polarstern begins the Antarctic season

What does it look like below the ice shelf of the calved massive iceberg A68?

On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.

Im Focus: Penn engineers develop ultrathin, ultralight 'nanocardboard'

When choosing materials to make something, trade-offs need to be made between a host of properties, such as thickness, stiffness and weight. Depending on the application in question, finding just the right balance is the difference between success and failure

Now, a team of Penn Engineers has demonstrated a new material they call "nanocardboard," an ultrathin equivalent of corrugated paper cardboard. A square...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

European Space Talks: Weltraumschrott – eine Gefahr für die Gesellschaft?

23.10.2018 | Event News

 
Latest News

Good preparation is half the digestion

16.11.2018 | Life Sciences

Microscope measures muscle weakness

16.11.2018 | Life Sciences

NASA keeps watch over space explosions

16.11.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>