heretical idea that prions - naked protein particles without a point of genetic material - may cause heritable disorders such as mad cow and Creutzfeldt-Jakob disease (CJD) in people has received a boost. In tomorrow's issue of Science , a team led by Glenn Telling and Stanley Prusiner of the University of California, San Francisco, provides compelling new evidence that may help explain how prions, that seem to exist in several strains, each with different characteristics, can transmit reproducible stress -. an apparent impossibility of an infectious agent that lack any genetic material
previous work of Prusiner team and others have shown that prions are made of a cellular protein that misfolded into a form abnormal. This can occur, for example, if the normal prion protein (PrP) in contact with an abnormal version, which then requires that misfold also. Over the past two years, other researchers, the study of prion disease called transmissible spongiform mink had provided evidence that different prion strains consist simply forms differently misfolded prion protein, each of which can transmit its own shape, or conformation, normal PrP. Now Telling, Prusiner and colleagues have extended the work to human prion in a mouse model.
They injected a special breed of transgenic mice with extracts of patients who died of brain or CJD or other prion disease, fatal familial insomnia. Prions responsible for both diseases have been known to bend differently because they produce fragments of different size when cut by an enzyme protein-splitting - an indication that the various amino acids are exposed on their surfaces. The team found that prion Prusiner produced in mice produce the same sized fragments that mothers molecules used for injections. The results are "a very powerful piece of support for the idea that abnormal protein can confer its abnormal configuration of the host prion protein," says neurologist Dennis Choi, of Washington University in St. Louis.
Not everyone is convinced by the results, however, mainly because of the difficulty to eliminate the possibility that a more conventional pathogen such as a virus could be lurking in the injected material. "The group took a [brain] extract relatively crude," said Michael Harrington, who studies diseases of the nervous system in Calfornia Institute of Technology in Pasadena. Therefore, it concludes that the work "does not confirm" that protein folding differences amounts to different strains. But Prusiner and his colleagues, the failure of years of research to the finger of a virus in prion diseases is proof that person is involved. "There is nothing to tell [people who think viruses cause the diseases] except that the evidence is overwhelming, "Prusiner maintains.
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