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| Monterotondo/Göttingen, 6 August 2006 |
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| Alleviating the burden of Multiple Sclerosis
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Researcher Manolis Pasparakis at the EMBL Mouse Biology Unit in
Monterotondo, Italy. |
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Researchers discover a cellular signal that aggravates the symptoms of MS
and might be targeted in new therapeutic approaches
Press
Release 6 August 2006 [PDF]
Deutsch
Italiano [PDF]
Depression, coordination
and speech problems, muscle weakness and disability are
just a few of the symptoms of Multiple Sclerosis [MS].
Researchers from the Mouse Biology Unit of the European
Molecular Biology Laboratory [EMBL] in Italy and the
Department of Neuropathology at the Faculty of Medicine,
University of Göttingen, Germany, have now discovered that
these symptoms are aggravated by a specific signal in cells in the
nervous system. The study, which will appear in this week's
online issue of Nature Immunology, suggests that blocking the
proteins that regulate the signal might be an efficient strategy for
new therapies against MS.
Nerve cells in our brain and spinal cord communicate with each
other using electrical signals. This communication is fast and efficient
because – just like wires in an electrical circuit – the axons of
our nerves are surrounded by an insulating layer. In MS this protective
sheath, made up of a mixture of lipids and proteins called
myelin, gets destroyed by cells of our own immune system, and
the communication between nerve cells gets disrupted. A central
player in the molecular mechanisms behind MS is a signaling
molecule called NF-kB.
"We have known for a long time that NF-kB is crucially involved
in MS," says Manolis Pasparakis, a former Group Leader at
EMBL's Mouse Biology Unit who now works as a Professor at the Institute
for Genetics at the University of Cologne, "but until now it was
not clear if it was friend or foe. We were not sure whether it protects
the brain cells against the consequences of the disease or
actually aggravates the damage."
To get a clear picture of NF-kB's role in MS, Pasparakis and his
scientific collaborators at the University of Göttingen investigated
what happens to mice with an MS-like condition if the action
of NF-kB is blocked. To shut down the signal they inactivated
IKK2 and NEMO, two proteins that activate NF-kB.
"This was quite a challenge because NF-kB is involved in many
crucial processes throughout the entire body, and shutting down
its activation in all cells kills the mouse before it is born," says
Pasparakis, "To observe the effect of NF-kB in MS, we used
sophisticated genetic techniques to generate mice that do not
express IKK2 and NEMO in brain cells only."
The results were mice that showed much milder MS symptoms
than normal, an effect that is very likely to be linked to the lower
amount of inflammatory messengers produced by their brain
cells.
"NF-kB regulates the production of messengers that are released
during inflammation to recruit and activate immune cells," says
Marco Prinz, whose group at the University of Göttingen collaborated
in the research. "Generally this is a good strategy to protect
the body from infections. But in MS it is exactly these immune
cells that cause the problem and their hyperactivation through
NF-kB only makes the situation worse."
Blocking IKK2 and NEMO interfered with this pathological
action of NF-kB and alleviated the symptoms of MS. This makes
the proteins promising as potential drug targets for new therapies
against the disease. The human NF-kB signaling network is very
similar to that of mice, so that compounds that inhibit IKK2 and
NEMO are likely to lead to the same alleviation of symptoms in humans.
Source Article
G. van Loo, M. Prinz, M. Pasparakis et al. NF-kB inhibition in the central nervous system ameliorates autoimmune encephalomyelitis
in mice, Nature Immunology, 6 August 2006
Press Contact
Anna-Lynn Wegener
Press Officer
EMBL Heidelberg
Tel: +49 +6221 387-8452
Email: wegener@embl.de |
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