Navigation Links
Selectively blocking inflammatory signals may protect mice from MS

A new way to preserve the cells that surround and protect nerves could lead to new treatments for demyelinating diseases such a multiple sclerosis, a research team reports in the May 10, 2006, issue of the Journal of Neuroscience.

The approach grew out of a novel explanation, quickly gaining followers, for the mechanism of nerve damage caused by multiple sclerosis. Instead of concentrating on the alterations that result in autoimmune assaults on the nervous system, researchers led by Brian Popko of the University of Chicago have focused on a set of factors that prevent recovery from the inflammatory attacks.

A series of papers from Popko's lab has demonstrated that interferon-gamma -- a chemical signal used to activate the immune system -- plays a critical role in damaging the cells that produce myelin, the protective coating that lines healthy nerves. Interferon not only leaves these cells, called oligodendrocytes, incapable of repairing the damage but can also kill them directly.

"Interferon-gamma is not normally found in the nervous system," said Popko, the Jack Miller Professor of Neurological Diseases at the University of Chicago, "but it can gain entry after an inflammatory flare-up. We previously showed how it harmed oligodendrocytes. Here we confirm its direct harmful effects on those cells and demonstrate one way of protecting them."

The researchers produced a series of transgenic mice. In one set they introduced genes that produced interferon-gamma within the central nervous system. In another set they also introduced a gene (known as suppressor of cytokine signaling 1, or SOCS1) that blocked the response of myelin-producing cells to interferon-gamma.

Although transgenic mice with low levels of interferon-gamma showed no symptoms of nervous system damage, 18 out of 20 mice exposed to higher interferon levels developed difficulty walking, including mild to moderate tremors, within two weeks of birth. Only four o ut of 20 mice with both high interferon levels and the SOCS1 gene had symptoms.

On autopsy, mice with high interferon levels in the nervous system had severe loss of oligodendrocytes, ranging from 20 to 40 percent. Those with the protective SOCS1 gene lost only eight to 15 percent.

High interferon levels were also associated with loss of myelin sheaths around nerve connections and unprotected axons in the brain. Again, SOCS1 was able to reduce the damage.

"Together," the researchers wrote, "these data demonstrate that oligodendroglial expression of SOCS1 protects mice from the clinical and morphological consequences of IFN-gamma expression in the central nervous system during development."

"We found this tremendously encouraging," said Popko. "SOCS1 prevented or reduced the harmful effects of interferon gamma on myelin-producing cells. This study solidifies our suspicions about interferon's specific role in demyelinating disease and suggests ways to block it."

Although there is currently no reliable way to deliver SOCS1 directly to the nerves of a patient with multiple sclerosis, this protective approach could be combined with stem cell therapy to repair nerve damage. Several research groups are already studying the use of stem cells to repair damaged myelin sheaths, but in the long term those stem cells would be vulnerable to ongoing immune-mediated damage.

But if stem cells could be engineered to resist harmful signals such as interferon-gamma, they might be protected from the "harsh environment" present in immune mediated demyelinated lesions, said Popko.


'"/>

Source:University of Chicago Medical Center


Related biology news :

1. UCSD study clarifies insulins role in blocking release of energy in patients with type II diabetes
2. Signal protein shows promise for blocking tumor promoters in skin cells
3. New compound prevents alcoholic behavior, relapse in animals by blocking stress response
4. Researchers report new pro-inflammatory role for anti-inflammatory enzyme
5. Scientists at Galileo Pharmaceuticals confirm inflammatory response linked to glucose levels
6. Protein finding could lead to treatment for inflammatory diseases
7. A Jekyll and Hyde of cytokines: IL-25 both promotes and limits inflammatory diseases
8. Anti-inflammatory drugs potentially deadly side effect found to be rare
9. Plants respond similarly to signals from friends, enemies
10. Edible bivalves as a source of human pathogens: signals between vibrios and the bivalve host.
11. Scientists discover that three overlapping signals in embryo help get the backbone right
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/28/2016)... First quarter 2016:   , Revenues amounted ... quarter of 2015 The gross margin was 49% (27) ... the operating margin was 40% (-13) Earnings per share ... operations was SEK 249.9 M (21.2) , Outlook   ... M. The operating margin for 2016 is estimated to ...
(Date:4/26/2016)... , April 27, 2016 ... the  "Global Multi-modal Biometrics Market 2016-2020"  report to ... ) , The analysts forecast the ... CAGR of 15.49% during the period 2016-2020.  ... number of sectors such as the healthcare, BFSI, ...
(Date:4/15/2016)... 15, 2016  A new partnership announced today ... underwriting decisions in a fraction of the time ... and high-value life insurance policies to consumers without ... With Force Diagnostics, rapid testing (A1C, Cotinine and ... (blood pressure, weight, pulse, BMI, and activity data) ...
Breaking Biology News(10 mins):
(Date:5/27/2016)... City, Missouri (PRWEB) , ... May 27, 2016 , ... ... Development Manager, Turf and Ornamental Products. , In his 15-year career with PBI-Gordon, Dave ... Herbicide Product Manager, where he was integral in the development and launch of many ...
(Date:5/27/2016)... NEW YORK , May 27, 2016 ... state, but investors playing in this space know that volatility ... this morning,s featured companies on ActiveWallSt.com: Synta Pharmaceuticals Corp. (NASDAQ: ... CTIC ), Lpath Inc. (NASDAQ: LPTN ), and ... now and gain access to the technical alerts for these ...
(Date:5/26/2016)... , May 26, 2016 Q BioMed ... it will be a featured presenter at the 5th Annual ... New York City at the Grand Hyatt ... , Q BioMed Inc. CEO, is scheduled to begin at ... the company,s business strategy, recent developments and outline milestones for ...
(Date:5/26/2016)... ... 26, 2016 , ... Kinder Scientific (KinderScientific.com), a leading animal ... the Company for the future. Kinder Scientific announces restructured ownership and additional ... appointed Chairman of the Board, Curtis D. Kinghorn has been appointed CEO/President and ...
Breaking Biology Technology: