proteoglycans

Unlocking the potential of stem cells to repair brain damage

A QUT scientist is hoping to unlock the potential of stem cells as a way of repairing neural damage to the brain.

Rachel Okolicsanyi, from the Genomics Research Centre at QUT’s Institute of Health and Biomedical Innovation, said unlike other cells in the body which were able to divide and replicate, once most types of brain cells died, the damage was deemed irreversible.

Ms Okolicsanyi is manipulating adult stem cells from bone marrow to produce a population of cells that can be used to treat brain damage.

"My research is a step in proving that stem cells taken from the bone marrow can be manipulated into neural cells, or precursor cells that have the potential to replace, repair or treat brain damage," she said.

Ms Okolicsanyi’s research has been published in Developmental Biology journal, and outlines the potential stem cells have for brain damage repair.

"What I am looking at is whether or not stem cells from the bone marrow have the potential to differentiate or mature into neural cells," she said.

"Neural cells are those cells from the brain that make everything from the structure of the brain itself, to all the connections that make movement, voice, hearing and sight possible."

Ms Okolicsanyi’s research is looking at heparin sulfate proteoglycans - a family of proteins found on the surface of all cells.

"What we are hoping is that by manipulating this particular family of proteins we can encourage the stem cells to show a higher percentage of neural markers indicating that they could mature into neural cells rather than what they would normally do, which is form into bone, cartilage and fat," she said.

"We will manipulate these cells by modifying the surrounding environment. For example we will add chemicals such as complex salts and other commonly found biological chemicals to feed these cells and this will either inhibit or encourage cellular processes."

Ms Okolicsanyi said by doing this, it would be possible to see the different reactions stem cells had to particular chemicals and find out whether these chemicals could increase or decrease the neural markers in the cells.

"The proteins that we are interested in are almost like a tree," she said.

"They have a core protein that is attached to the cell surface and they have these heparin sulfate chains that branch off.

"So when the chemicals we add influence the stem cell in different ways, it will help us understand the interactions between proteins and the resulting changes in the cell.

"In the short-term it is proof that simple manipulations can influence the stem cell and in the long-term it is about the possibility of increasing the neural potential of these stem cells."

Ms Okolicsanyi said the big picture plan was to be able to introduce stem cells into the brain that would be able to be manipulated to repair damaged brain cells.

"The idea, for example, is that in stroke patients where the patient loses movement, speech or control of one side of their face because the brain’s electrical current is impaired, that these stem cells will be able to be introduced and help the electrical current reconnect by bypassing the damaged cells."

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Receptor may aid spread of Alzheimer’s and Parkinson’s in brain

Scientists at Washington University School of Medicine in St. Louis have found a way that corrupted, disease-causing proteins spread in the brain, potentially contributing to Alzheimer’s disease, Parkinson’s disease and other brain-damaging disorders.

Image: An electron micrograph shows clumps of corrupted tau protein outside a nerve cell. Scientists have identified a receptor that lets these clumps into the cell, where the corruption can spread. Blocking this receptor with drugs may help treat Alzheimer’s, Parkinson’s and other disorders.

The research identifies a specific type of receptor and suggests that blocking it may aid treatment of theses illnesses. The receptors are called heparan sulfate proteoglycans (HSPGs).

“Many of the enzymes that create HSPGs or otherwise help them function are good targets for drug treatments,” said senior author Marc I. Diamond, MD, the David Clayson Professor of Neurology. “We ultimately should be able to hit these enzymes with drugs and potentially disrupt several neurodegenerative conditions.”

The study is available online in the Proceedings of the National Academy of Sciences.

Over the last decade, Diamond has gathered evidence that Alzheimer’s disease and other neurodegenerative diseases spread through the brain in a fashion similar to conditions such as mad cow disease, which are caused by misfolded proteins known as prions.

Proteins are long chains of amino acids that perform many basic biological functions. A protein’s abilities are partially determined by the way it folds into a 3-D shape. Prions are proteins that have become folded in a fashion that makes them harmful.

Prions spread across the brain by causing other copies of the same protein to misfold.

Among the most infamous prion diseases are mad cow disease, which rapidly destroys the brain in cows, and a similar, inherited condition in humans called Creutzfeldt-Jakob disease.

Diamond and his colleagues have shown that a part of nerve cells’ inner structure known as tau protein can misfold into a configuration called an amyloid. These corrupted versions of tau stick to each other in clumps within the cells. Like prions, the clumps spread from one cell to another, seeding further spread by causing copies of tau protein in the new cell to become amyloids.

In the new study, first author Brandon Holmes, an MD/PhD student, showed that HSPGs are essential for binding, internalizing and spreading clumps of tau. When he genetically disabled or chemically modified the HSPGs in cell cultures and in a mouse model, clumps of tau could not enter cells, thus inhibiting the spread of misfolded tau from cell to cell.

Holmes also found that HSPGs are essential for the cell-to-cell spread of corrupted forms of alpha-synuclein, a protein linked to Parkinson’s disease.

“This suggests that it may one day be possible to unify our understanding and treatment of two or more broad classes of neurodegenerative disease,” Diamond said. 

“We’re now sorting through about 15 genes to determine which are the most essential for HSPGs’ interaction with tau,” Holmes said. “That will tell us which proteins to target with new drug treatments.”

Make Perfect Bone Broth: 3 Tips From The Expert We Trust Most

There are countless ways to improve your health, but sipping on bone broth is one practice that’s been all over our radar lately. Bone broth has deeply nourishing and healing properties that are missing from many of our modern diets. It is rich in gelatin, essential amino acids such as glycine, proline and glutamine, vitamins, minerals, and essential healing sugars known as proteoglycans. Through these nutrients, bone broth can improve sleep quality, lessen fatigue, boost well-being, stimulate cartilage production and inhibit cartilage degradation. Its amino acids are also essential for healthy skin and connective tissue and for maintaining muscle-tissue mass. As if that wasn’t enough, it’s an excellent source of collagen as well. Collagen is a vital building block of tendons, ligaments, arteries, veins, and muscles - including the heart muscle. It keeps our tissues strong and elastic, helping to reduce the aging of skin (think sagging and wrinkling), and keeps our joints flexible. It is an important component of wound healing and the building of cartilage, making it a great food for preventing osteoarthritis. Incorporating bone broth into your daily routine is simple: with a bit of foresight, a large enamel stockpot, this recipe, and the following three essential tips from the Nourishing Broth cookbook, you’ll be trading in your ritual cup of coffee for a pipping hot mug of bone broth in no time:

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Make Perfect Bone Broth: 3 Tips From The Expert We Trust Most

Make Perfect Bone Broth: 3 Tips From The Expert We Trust Most

There are countless ways to improve your health, but sipping on bone broth is one practice that’s been all over our radar lately. Bone broth has deeply nourishing and healing properties that are missing from many of our modern diets. It is rich in gelatin, essential amino acids such as glycine, proline and glutamine, vitamins, minerals, and essential healing sugars known as proteoglycans.…

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