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【bio-news】Science：重建损伤神经的新希望
http://www.sciencedaily.com/releases/2009/01/090122141144.htm
All three photos show severed nerves from nematode worms. Axons -- the wiry part of nerve cells -- had stretched from top to bottom but were cut by a laser beam. In each case, the "stump" of the severed nerve hangs downward from the top. In the left image, the nerve regeneration gene dlk-1 operates normally -- which means not very well -- so the upward-growing axon branches too much and lacks what is known as a "growth cone," so it never reaches the major nerve that runs horizontally near the top of each image. In the center photo, the regeneration gene has been over-activated, so it grows upward with a normal growth cone and not too many branches, allowing it to eventually reach the major nerve. The right image shows the severed nerve in a worm in which the regeneration gene was crippled, so there is no regeneration of the nerve axon, just stumps at top and bottom. (Credit: Michael Bastiani, University of Utah)
ScienceDaily (Jan. 26, 2009) — University of Utah scientists identified a worm gene that is essential for damaged nerve cells to regenerate, and showed they could speed nerve regeneration by over-activating the gene – a step toward new treatments for nerves injured by trauma or disease.
Oddly, the gene and a related "pathway" – a chain of molecular events – is not required for normal nerve development in embryos, the researchers report in the Jan. 22 issue of Science Express, the online edition of the journal Science.
"We discovered a molecular target for a future drug that could vastly improve the ability of a neuron to regenerate after injury," either from trauma or disease, says biology Professor Michael Bastiani, leader of the research team and a member of the Brain Institute at the University of Utah.
Study coauthor and biology Professor Erik Jorgensen – the Brain Institute's scientific director – says: "In the future, we would like to develop drugs that could activate this chain of molecular events in nerve cells and stimulate regeneration of diseased and injured nerve cells. At this point, we can't do that. But this study gives us hope that in the future, we will have a rational approach for stimulating regeneration."
"Eventually, this may be a way to treat spinal cord injuries," adds study coauthor Paola Nix, a biology research associate.
Bastiani says an ability to stimulate nerve regeneration one day also may help treat multiple sclerosis, in which nerves are damaged by loss of their myelin coating.
He says the study used nematode worms, which "have the same molecules performing similar functions in humans. We found a pathway that not only regenerates nerves in the worm but also exists in humans, and we think it serves the same purpose."
Nix adds: "The next thing to do would be to test this gene in [other] animals and eventually humans to see if it plays the same role."
The core of the molecular chain of events involves four genes. The most important is dlk-1¸ which is known as a "MAP kinase kinase kinase" or MAPKKK. When the Utah scientists "overexpressed" the dlk-1 gene in worms – making it more active than normal – broken nerves in the worms regenerated much more quickly than expected. When dlk-1 was blocked, regeneration did not occur.
The study's other authors were Marc Hammarlund, a former University of Utah postdoctoral researcher now at Yale University, and lab technician Linda Hauth.
The research was funded initially by the Craig H. Neilsen Foundation, and the scientists dedicated it to Neilsen, a Utah native and chairman of Ameristar Casinos. Neilsen was paralyzed by a spinal cord injury during a 1985 car wreck. He funded the project in hope of finding a cure. He died in 2006, while the study was underway.
Searching for Nerve Regeneration Genes
Nerve cells have the ability to regenerate in the embryo, but lose the ability as an organism ages. Most adult nerve cells "regenerate poorly or not al all," the researchers write, although peripheral nerve cells – like those in the arms and legs – regenerate better than central nervous system neurons in the brain and spinal cord. No one knows why.
The new study focused on regeneration of motor neuron axons – the wiry part of every nerve cell that transmits signals to other nerve cells or to cells such as muscle.
The research team developed a "genetic screen" to look for genes involved in nerve regeneration. They mutated a worm gene that produces a protein named beta spectrin, which helps keep nerve cells flexible. Mutant worms lacked beta spectrin, so their nerves broke as they crawled around a culture dish.
Te scientists used a method named RNA interference to suppress the functioning of 5,000 of the 20,000 worm genes – one at a time. People also have those 5,000 genes.
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作者:admin@医学,生命科学 2011-02-20 05:11
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