New point of focus found for the treatment of Rheumatoid Arthritis and other autoimmune diseases
Scientists affiliated with VIB and UGent have discovered a mechanism used by the protein A20 to combat inflammation. This could be a very important point of focus in the search for a treatment for autoimmune diseases such as Rheumatoid Arthritis, in which the patient suffers from chronic, uncontrolled inflammation.
Rudi Beyaert: "We hope that our research can eventually contribute
to the development of new therapies against Rheumatoid Arthritis
and other auto-immune conditions.”
A20, a protein involved in Rheumatoid Arthritis (RA) and other
autoimmune conditions
RA is a chronic progressive joint condition that starts with an
inflammation of the joint membrane and affects the soft tissues
around the joints. In Belgium, the number of RA patients is
estimated at 100,000. The actual cause is unknown, but there is
evidence that the immune system is disrupted, which causes the body
to attack its own tissues and creates inflammation in various
joints.
Rudi Beyaert and his research team previously identified the
molecule A20 as an important point of focus for the development of
new medicines against RA and other autoimmune diseases. A20 appears
to exert an anti-inflammatory effect in white blood cells.
Unraveling the details of an interaction
For the development of new medicines, it is important to fully
understand the anti-inflammatory effect of A20. Previous research
has demonstrated that A20 interferes with specific “signaling
pathways” in our cells that stimulate the activity of a DNA
binding molecule (NF-κB). NF-κB plays a key role in
many immunological processes and excessive activation of
NF-κB can result in a whole range of “inflammatory
diseases”, including arthritis. However, it is still largely
unknown how A20 interferes with the activity of NF-κB.
Kelly Verhelst and other scientists in the team of Rudi Beyaert
have now mapped the specific interaction between A20 and the
NF-κB “signaling pathway”. They demonstrated that
a small particle (ZF7) at the end of the A20 protein binds to
certain small molecules (ubiquitin chains), which are attached to
specific NF-κB signaling proteins in the cell. This makes it
impossible for these proteins to communicate with other proteins,
thereby disrupting the signal that would normally result in
inflammation.
Research impact
This is very interesting from a scientific point of view, because
the VIB scientists have identified a new mechanism that brings us
one step closer to the possible development of a new medicine.
After all, we now know which part of A20 has an anti-inflammatory
effect and how exactly this works. Rudi Beyaert: “Now that we
know the importance of this small fragment (ZF7) of A20 for the
anti-inflammatory effect, we can also use it as a point of focus
for the development of medicines against various auto-immune
diseases. This is one step closer, but we still have a long way to
go.”
Questions
As this research may raise many questions, we ask you to refer in
your report or article to the e-mail address that people can use if
they have questions: patients@vib.be
Relevant scientific publication
The research was published in the leading journal “The EMBO
Journal”
Verhelst et al.,
A20 inhibits LUBAC-mediated NF-κB activation by binding
linear polyubiquitin chains via its zinc finger 7
Research team
This research was performed by the research team led by Rudi
Beyaert in the VIB Department of Molecular Biomedical Research,
UGhent.
Funding
This research was jointly funded by:
VIB, FWO, IWT, Belspo, and UGhent
For all press inquiries, contact
Mrs. Kris Van der Beken
VIB Communications Manager
mob: +32 473 78 34 35 kris.vanderbeken@vib.be
Posted: October 2012
