More than 11,000 Americans suffer spinal cord injuries each year, and since over a quarter of those injuries are due to falls, the number is likely to rise as the population ages.
The reason so many of those injuries are permanently disabling is that the human body lacks the capacity to regenerate nerve fibers. The best our bodies can do is route the surviving tissue around the injury site.
"It's like a detour after an earthquake," says Kuo-Fen Lee, the Salk Institute's Helen McLoraine Chair in Molecular Neurobiology. "If the freeway is down, but you can still take the side-streets, traffic can still move. So your strategy has to be to find a way to preserve as much tissue as possible, to give yourself a chance for that rerouting."
In a paper published in this week's PLOS ONE, Lee and his colleagues describe how a protein named P45 may yield insight into a possible molecular mechanism to promote rerouting for spinal cord healing and functional recovery. Because injured mice can recover more fully than human beings, Lee sought the source of the difference. He discovered that P45 had a previously unknown neuroprotective effect.
"As a biochemist and neurobiologist, this discovery gives me hope that we can find a potential target molecule for drug treatments," says Lee. "Nevertheless, I must caution that this is only the first step in knowing what to look for."In a human or a mouse, the success of an attempted rerouting after a spinal cord injury depends on how much healthy tissue is left. But wounds set off a cascade of reactions within cells, which if not stopped in time will result in more dead and dying tissue extending beyond the injury site. Nerve traction from the injury site leads to disconnection of the network required for normal sensory and motor functions. Lee found that P45 is the key factor determining whether the cascade continues on to its destructive end.
But there's more to how P45 works that gives Lee hope that he may be on to a unique approach to finding new ways to treat spinal cord injuries. In other recent findings, which are being prepared for publication, his team saw P45 also yield positive effects, specifically the encouragement of healthy tissue growth. Thus, Lee concludes its real role may be as a sort of "see-saw" molecule that tips the balance in the cascade from negative to positive.
"The great thing about P45 is that it can both inhibit the negative by blocking the conformational change that would lead to more cell death, while promoting the positive-the survival and growth of tissue-thus making it easier to foster recovery following spinal cord injury," Lee explains.
"If you can understand where you could tilt the balance of positive/negative signal, it would give you less damage while helping to promote healing," says Lee. "It could be combinatorial-maybe one molecule can do both, or maybe it's a combination of two molecules, one to negate, one to promote. The hope is if such a control switch could be found, more tissue could be preserved at the site of injury, thus increasing the chances that movement might someday be restored."
The next step for Lee's laboratory will be to seek either a gene, or a process that works in a similar see-saw way in humans, or can be made to work with therapeutic intervention. Still, Lee cautions, this remains a proof of concept experiment in mice. Even if such a mechanism were found in humans, clinical applications would be years away.
Other researchers on the study were Tsung-Chang Sung, Zhijiang Chen, Sandrine Thuret, Marçal Vilar, Fred H. Gage and Roland Riek of the Salk Institute.
This work was supported by the National Institutes of Health, National Institute of Aging, MDA, Clayton Foundation, Paralyzed Veterans of America Spinal Cord Research Foundation, the Paralysis Project of America, Christopher and Dana Reeve Foundation, Ministerio de Economia y Competitividad and the Institute of Health Carlos III.
Kat Kearney | EurekAlert!
Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania
The strange double life of Dab2
10.01.2017 | University of Miami Miller School of Medicine
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.
The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
17.01.2017 | Earth Sciences
17.01.2017 | Materials Sciences
17.01.2017 | Architecture and Construction