|MadSci Network: Biochemistry|
In your question, you asked about detecting prion proteins that are “mutated.” This term usually refers to a mistake in the DNA sequence that encodes a protein. This is not the case for prions. They are normal proteins that become mis-folded. The mis-folded protein then stimulates the mis-folding of normally-folded versions of itself, thus propagating the mis-folding. The proliferating mis-folded prion proteins are resistant to degradation by enzymes that would normally do this, and they accumulate in the central nervous system, causing chronic, and eventually fatal brain degeneration. This, and not the absence of the normally folded version, is the cause of the disease. If an animal or person eats tissues containing the misfolded prion protein, disease can be transmitted. This is the only “infectious” disease that does not involve DNA or RNA, just protein, and for his decades-long investigations that established this radical concept, Stanley Prusiner was recently awarded a Nobel prize.
Tests have to be able to discriminate between the normally and the abnormally folded versions of the protein. There are such tests for BSE and CJD. They are based on antibodies that recognize the difference. Typically, brain tissue is homogenized, separated on a gel, blotted onto a polymer sheet, and probed with antibody. This is called a “western blot.” There is also a rapidly growing number of research papers that describe other methods for doing this, some faster, cheaper, more sensitive, able to work with less tissue, different tissues such as lymph nodes, and even a new test that can detect the normal prion protein in urine, although its usefulness in detecting disease is not known. Obviously, taking out pieces of brain for analysis is not the ideal type of test, especially if one wants to identify infected animals or people before they become symptomatic! I anticipate that there will be continued, rapid growth in the range and sensitivity of these other types of test, as there are extremely strong public health and economic pressures to do so.
I hope this answers your question.
Paul R. Odgren, Ph.D. Dept. of Cell Biology University of Massachusetts Medical School
Try the links in the MadSci Library for more information on Biochemistry.