Molecule that Blocks Healing for Some Brain Injuries New Target for Drugs
“This study uncovers a new player in white matter disease and identifies a potential drug target,” said Jim Koenig, Ph.D., program director at NINDS. “It also describes a unique situation in which the brain tries to take over immune system functions, with devastating results.”
A specific fragment of hyaluronic acid may trigger a sequence of events preventing myelin repair in chronic white matter injury.
Image courtesy of Stephen Back, M.D., Ph.D., Oregon Health & Science University.
A team led by Stephen Back, M.D., Ph.D., professor of pediatrics and neurology at the Oregon Health & Science University in Portland, took a detailed look at the HA fragments to see how they block myelin repair. Using state-of-the-art techniques, Dr. Back and his colleagues were able to create HA fragments of different sizes.
Results showed that only one specific size of HA, the 210 kDa fragment, had an effect on OPC proliferation.
Dr. Back and his team treated rat cells that mimicked white matter disease with the 210 kDa HA fragment. They discovered that the HA initially turned on molecules associated with myelination but then shut them down completely, a strategy that is similar to immune tolerance, which is used by the immune system to prevent severe tissue injury from an ongoing, damaging response to bacteria and viruses.
“We showed that HA creates not just a roadblock to myelin repair after injury, it also shuts down all of the possible detours,” said Dr. Back. “Tolerance can be helpful in preventing the brain from repairing itself too quickly, but in some disease conditions, it can turn into a detrimental response.”
Dr. Back and his team also discovered that the 210 kDa fragment signals to TLR4, a protein that oversees immune tolerance, to activate FoxO3, which helps control the activity of genes involved in myelin repair. This activation of FoxO3 eventually leads to a decrease in the activity of myelin-related genes and a slowdown in white matter repair. However, this process only takes place if HA is present.
When Dr. Back and his group looked at human brain tissue affected by white matter injury and multiple sclerosis, they found activated FoxO3 in OPCs that were blocked from producing myelin.
In the brain, the large, intact HA makes up most of the extracellular matrix, the substance found between cells. Damage to the extracellular matrix leads to inflammation and this can occur in white matter injury.
“For decades HA was thought of as simply a glue holding everything together. In recent years, we have come to learn how critical this molecule is for various pathways and potentially, many neurological disorders,” said Dr. Back.
More research is needed to learn about the molecules involved in white matter repair as well as the role of different HA fragments in these processes.
The study was funded by NINDS (NS054044, NS045737), the National Institute on Aging (AG31892), American Stroke Association, Congressionally Directed Medical Research Programs (MS160144) and the National Multiple Sclerosis Society.
Contacts and sources:
Barbara McMakin
National Institutes of Health (NIH)
Source:
Anyone can join.
Anyone can contribute.
Anyone can become informed about their world.
"United We Stand" Click Here To Create Your Personal Citizen Journalist Account Today, Be Sure To Invite Your Friends.
Please Help Support BeforeitsNews by trying our Natural Health Products below!
Order by Phone at 888-809-8385 or online at https://mitocopper.com M - F 9am to 5pm EST
Order by Phone at 866-388-7003 or online at https://www.herbanomic.com M - F 9am to 5pm EST
Order by Phone at 866-388-7003 or online at https://www.herbanomics.com M - F 9am to 5pm EST
Humic & Fulvic Trace Minerals Complex - Nature's most important supplement! Vivid Dreams again!
HNEX HydroNano EXtracellular Water - Improve immune system health and reduce inflammation.
Ultimate Clinical Potency Curcumin - Natural pain relief, reduce inflammation and so much more.
MitoCopper - Bioavailable Copper destroys pathogens and gives you more energy. (See Blood Video)
Oxy Powder - Natural Colon Cleanser! Cleans out toxic buildup with oxygen!
Nascent Iodine - Promotes detoxification, mental focus and thyroid health.
Smart Meter Cover - Reduces Smart Meter radiation by 96%! (See Video).