Nerves under control

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Nerves under control

http://www.ethlife.ethz.ch/archive_articles/100512_Myelinkontrolle_cm/index_EN

The proper transmission of nerve signals along body nerves requires an

insulation layer, named myelin sheath. To be efficient this sheath is designed

to have a certain thickness and researchers from the ETH Zürich have now

discovered that proteins Dlg1 and PTEN interact to control the myelin sheath

thickness. Recently published in Science their discovery improves our

understanding of Charcot-Marie-Tooth neurodegenerative diseases and open a new

avenue in the potential treatment of these incurable and debilitating diseases.

Nerve fibre during signal transmission. A crucial factor in the transmission of

nerve signals is the myelin layer – also known as the myelin sheath – which

surrounds the axons. Axons are nerve cell projections through which the signals

are relayed; the myelin sheath is formed by the Schwann cells in the peripheral

nervous system, i.e. in the nervous system outside the brain and spinal chord.

If it is too thick or too thin, the signal transmission slows down; if the

myelin sheath becomes too badly damaged, it can cause diseases like

Charcot-Marie-Tooth diseases. Patients suffer from an increasing weakness of the

hands and feet, which gradually spreads to the arms and legs, sometimes even

making them wheelchair-bound for the rest of their lives.

But which molecules regulate the thickness of the myelin sheath? Scientists at

ETH Zurich from the research groups around biologists Ueli Suter and Nicolas

Tricaud set about finding out. They have now published their findings in an

online article in the journal Science[1].

The scientists didn't have to start their search entirely from scratch, however,

having already developed a mouse model for a sub-type of Charcot-Marie-Tooth

disease; the model is based upon a mutation in the gene for the protein MTMR2

and leads to hypermyelination by the Schwann cells. What's more, the researchers

already knew from other studies that MTMR2 interacts with Dlg1.

In experiments conducted on cell cultures and the sciatic nerve in mice, the

researchers were now able to demonstrate that Dlg1 inhibits myelin growth. For

this to work, however, it needs to enlist the help of another signal protein:

PTEN. Together, they ensure that the growth of the myelin sheath does not go to

excess in the mouse's development. If the brake is " released " by suppressing

Dlg1 or PTEN, it results in myelin excess that not only leads to an extra-thick

myelin sheath, but also to its degeneration.

This process is characteristic of various diseases of the peripheral nervous

system and , as it was revealed in the mouse model of Charcot-Marie-Tooth

disease the Dlg-PTEN brake no longer works in these diseases. Nicolas Tricaud is

convinced that the project helps to understand the basic molecular mechanisms of

myelination, as well as offering new opportunities to define how the

misdirection of these processes can cause neurodegenerative diseases and how

this might be remedied.

References

[1] Cotter L, Ozçelik M, C, Pereira JA, Locher V, Baumann R, Relvas JB,

Suter U, Tricaud N.: „Dlg1-PTEN Interaction Regulates Myelin Thickness to

Prevent Damaging Peripheral Nerve Overmyelination.» Science. 2010 May 6.