Corporate Banner
Satellite Banner
Scientific Community
Become a Member | Sign in
Home>News>This Article

Scientists Identify Key Biological Mechanism in Multiple Sclerosis

Published: Tuesday, December 04, 2012
Last Updated: Tuesday, December 04, 2012
Bookmark and Share
Imaging study finds potential new target to combat disease.

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, a professor in neurology at UCSF, 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.

MS, which afflicts more than two million people worldwide, develops when the body’s immune system attacks the brain. This attack damages nerve cells, leading to a host of symptoms including numbness, fatigue, difficulty walking, paralysis and loss of vision. While some drugs can delay these symptoms, they do not treat the disease’s underlying cause - which researchers are only just beginning to understand.

“To successfully treat MS, we must first identify what triggers the disease and what enables its progression,” said Akassoglou, who also directs the Gladstone Center for In Vivo Imaging Research. “Here, we have shown that the leakage of blood in the brain acts as an early trigger that sets off the brain’s inflammatory response - creating a neurotoxic environment that damages nerve cells.”

Akassoglou and her team reached this conclusion by using advanced imaging techniques to monitor the disease’s progression in the brain and spinal cord of mice modified to mimic the signs of MS.

Traditional techniques only show “snapshots” of the disease’s pathology. However, this analysis allows researchers to study individual cells within the living brain - and to monitor in real-time what happens to these cells as the disease worsens over time.

“In vivo imaging analysis let us observe in real-time which molecules crossed the blood-brain barrier,” said Dimitrios Davalos, PhD, Gladstone staff research scientist, associate director of the imaging center and the paper’s lead author. “Importantly, this analysis helped us identify the protein fibrinogen as the key culprit in MS, by demonstrating how its entry into the brain through leaky blood vessels impacted the health of individual nerve cells.”

Fibrinogen, a blood protein that is involved in coagulation, is not found in the healthy brain. In vivo imaging over different stages of disease revealed, however, that a disruption in the blood-brain barrier allows blood proteins - and specifically fibrinogen - to seep into the brain.

Microglia - immune cells that act as the brain’s first line of defense - initiate a rapid response to fibrinogen’s arrival. They release large amounts of chemically reactive molecules called ‘reactive oxygen species.’ This creates a toxic environment within the brain that damages nerve cells and eventually leads to the debilitating symptoms of MS.

Importantly, the team found a strategy to halt this process by genetically modifying fibrinogen in the animal models. This strategy disrupted the protein’s interaction with the microglia without affecting fibrinogen’s essential role as a blood coagulant.

In these models, the microglia did not react to fibrinogen’s arrival and did not create a toxic environment. As a result, the mice failed to show the type of progressive nerve cell damage seen in MS.

“Dr. Akassoglou’s work reveals a novel target for treating MS - which might protect nerve cells and allow early intervention in the disease process,” said Ursula Utz, PhD, MBA, a program director at the National Institutes of Health’s National Institute of Neurological Disorders and Stroke, which provided funding for this research.

“Indeed, targeting the fibrinogen-microglia interactions to halt nerve-cell damage could be a new therapeutic strategy,” said Akassoglou. “At present we are working to develop new approaches that specifically target the damaging effects of fibrinogen in the brain. We also continue to use in vivo imaging techniques to further enhance our understanding of what triggers the initiation and progression of MS.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Researchers Identify Protein Key in Proliferation of Lymphoma Cells
Inhibiting PERK protein could reduce formation of cancerous tumors.
Thursday, November 29, 2012
Well-Known Cell Protein Reveals New Tricks
Discovery of clathrin protein's key role in cell division could help understanding of cancer.
Wednesday, September 12, 2012
Scientific News
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Gut Microbes Signal to the Brain When They're Full
Don't have room for dessert? The bacteria in your gut may be telling you something.
Turning up the Tap on Microbes Leads to Better Protein Patenting
Mining millions of proteins could become faster and easier with a new technique that may also transform the enzyme-catalyst industry, according to University of California, Davis, researchers.
Exploring the Causes of Cancer
Queen's research to understand the regulation of a cell surface protein involved in cancer.
Measuring microRNAs in Blood to Speed Cancer Detection
A simple, ultrasensitive microRNA sensor holds promise for the design of new diagnostic strategies and, potentially, for the prognosis and treatment of pancreatic and other cancers.
Novel Proteins Linked to Huntington's Disease
University of Florida Health researchers have made a new discovery about Huntington's disease, showing that the gene that causes the fatal disorder makes an unexpected "cocktail" of mutant proteins that accumulate in the brain.
Enzyme Critical to Maintaining Telomere Length Discovered
New method expected to speed understanding of short telomere diseases and cancer.
New Method Identifies Up to Twice as Many Proteins and Peptides
An international team of researchers developed a method that identifies up to twice as many proteins and peptides in mass spectrometry data than conventional approaches.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos