Scientists identify key biological mechanism in MS

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Scientists identify key biological mechanism in MS

Postby MSUK » Thu Nov 29, 2012 11:57 pm

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Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.

Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3535
MS-UK - http://www.ms-uk.org/
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Re: Scientists identify key biological mechanism in MS

Postby Leonard » Fri Nov 30, 2012 4:34 am

squiffy2 wrote:Image

Scientists at the Gladstone Institutes have defined for the first time a key underlying process implicated in multiple sclerosis (MS)—a disease that causes progressive and irreversible damage to nerve cells in the brain and spinal cord. This discovery offers new hope for the millions who suffer from this debilitating disease for which there is no cure.

Researchers in the laboratory of Gladstone Investigator Katerina Akassoglou, PhD, have identified in animal models precisely how a protein that seeps from the blood into the brain sets off a response that, over time, causes the nerve cell damage that is a key indicator of MS. These findings, which are reported in the latest issue of Nature Communications, lay the groundwork for much-needed therapies to treat this disease.... Read More - http://www.msrc.co.uk/index.cfm/fuseact ... ageid/3535


I am sure that there are many things that are going wrong in the endothelium of MS patients.
This "key biological mechanism" may be just a tiny part of it..

A few days ago, this discovery by German scientists was unveiled:
Inhibitor of myelin formation identified
general-discussion-f1/topic21217.html
probably also a tiny part of the picture..

I think it works different.
When the Vit D receptor and other receptors are enabled again, 1000 or more genes will be transcribed again,
with effects on the organs, and also the nerves..
And the body will take metabolic control again..

I think looking into the huge complexity of our micro-cosmos and into the functioning of individual genes will not lead us to the solution.
I think medical researchers should look at a meta-level, how receptors are blocked or made to dysfunction, and what to do about that..
Last edited by Leonard on Fri Nov 30, 2012 9:22 am, edited 1 time in total.
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Re: Scientists identify key biological mechanism in MS

Postby cheerleader » Fri Nov 30, 2012 9:17 am

Fibrinogen was found to be the first invader to cross a broken blood brain barrier. It preceded demyelination, inflammation, and caused death of axons.

"Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation."
Just as Dr. Zamboni hypothesized in 2006 in his Big Idea paper, where he compared the MS process to that which he saw in chronic venous disease. Where fibrinogen initiated the degenerative process.

The FULL paper is online for free.
http://www.nature.com/ncomms/journal/v3 ... s2230.html

cheer
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dx dual jugular vein stenosis (CCSVI) 4/09
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Re: Scientists identify key biological mechanism in MS

Postby Leonard » Fri Nov 30, 2012 9:25 am

cheerleader wrote:Fibrinogen was found to be the first invader to cross a broken blood brain barrier. It preceded demyelination, inflammation, and caused death of axons.

"Fibrinogen-induced perivascular microglial clustering is required for the development of axonal damage in neuroinflammation."
Just as Dr. Zamboni hypothesized in 2006 in his Big Idea paper, where he compared the MS process to that which he saw in chronic venous disease. Where fibrinogen initiated the degenerative process.

The FULL paper is online for free.
http://www.nature.com/ncomms/journal/v3 ... s2230.html

cheer


Hi cheer,

the paper under the link mentions a receptor..

don't you think that we may be talking here potentially hundreds of receptors that control some metabolic processes?

and that we better start work on general receptor health?

Leo
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Re: Scientists identify key biological mechanism in MS

Postby cheerleader » Fri Nov 30, 2012 10:42 am

Hi Leonard--the integin receptor mentioned in the abstract is shown within the context of finding a pharmacological method of blocking fibrinogen from crossing the BBB.

Blood-brain barrier disruption, microglial activation and neurodegeneration are hallmarks of multiple sclerosis. However, the initial triggers that activate innate immune responses and their role in axonal damage remain unknown. Here we show that the blood protein fibrinogen induces rapid microglial responses toward the vasculature and is required for axonal damage in neuroinflammation. Using in vivo two-photon microscopy, we demonstrate that microglia form perivascular clusters before myelin loss or paralysis onset and that, of the plasma proteins, fibrinogen specifically induces rapid and sustained microglial responses in vivo. Fibrinogen leakage correlates with areas of axonal damage and induces reactive oxygen species release in microglia. Blocking fibrin formation with anticoagulant treatment or genetically eliminating the fibrinogen binding motif recognized by the microglial integrin receptor CD11b/CD18 inhibits perivascular microglial clustering and axonal damage. Thus, early and progressive perivascular microglial clustering triggered by fibrinogen leakage upon blood-brain barrier disruption contributes to axonal damage in neuroinflammatory disease.


This lab at UCSF has been working for over a decade on looking for a pharma solution to limit the damage from fibrinogen leakage into the brain. http://labs.gladstone.ucsf.edu/akassoglou
What Dr. Zamboni suggested in 2006 was that this fibrinogen leakage was also seen in chronic venous disease of the legs, and the way to stop it was to treat the underlying venous disease. Then, no fibrinogen leakage.

I guess it's the difference between searching for a molecular answer, as opposed to an underlying mechanical answer.
Or treatment vs. aetiology.
In any event, this research is still important, because it's focusing in on the order of destruction in the CNS in MS. And because fibrinogen appears to be the first invader, before the immune system and inflammation are activated---it further defines the link to the vascular theory.
cheer
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dx dual jugular vein stenosis (CCSVI) 4/09
http://ccsviinms.blogspot.com
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