"This evidence has led to the now widely accepted prion theory, which states that the cellular protein PrP is the sole causative agent of prion diseases; there is no nucleic acid involved. The theory holds that PrP is normally in a stable shape (pN) that does not cause disease. The protein can be flipped, however, into an abnormal shape (pD) that does cause disease. pD is infectious because it can associate with pN and convert it to pD, in an exponential process--each pD can convert more pN to pD.
"Prions can be transmitted, possibly by eating and certainly by inoculation either directly into the brain or into skin and muscle tissue. Exponential amplification of the prion (converting pN into pD in the body) would then result in disease. Occasional, sporadic cases of prion diseases arise in middle or old age, presumably because there is a very small but real chance that pN can spontaneously flip to pD; the cumulative likelihood of such a flip grows over the years. Inherited cases of CJD and GSS may result from mutations in the PrP gene, which gives rise to changes in the amino acid sequence of the PrP protein. This change would increase the probability of pN transforming into pD, so that the disease would almost certainly occur.
"Physical analysis of the structure of PrP provides some direct evidence for the existence of two different (normal and aberrant) shapes. Recently the structure of the core part of the PrP protein was determined by magnetic resonance image analysis. Mutations that cause prion disease are clustered within or adjacent to key structural elements in the protein, so it is easy to imagine that mutations destabilize the structure of pN and cause it to reconfigure into pD.
"The prion theory has not been proved correct, but much evidence now supports it. We do not yet know why the pD structure of a prion would result in neurodegeneration, but we do know that prion protein accumulates in brain tissue. One part of the prion protein can cause apoptosis, or programmed cell death; perhaps this mechanism explains the pattern of the disease.
"Prions have long intrigued scientists because of their unusual properties. Recently the general public has become interested in them as well because of the epidemic of BSE, more dramatically known as mad cow disease. Hundreds of thousands of infected animals have been eaten by Europeans and particularly the British over the past 10 years. The latest research suggests that the infected meat may pose a threat to human health, but the significance of that threat may not become apparent for years. Although it is generally considered a British problem, BSE is almost certainly a natural disease of cattle, so it is undoubtedly found in other countries as well. The normal incidence of BSE is vanishingly small, however. The U.S. Department of Agriculture claims that BSE has not been identified in any U.S. cattle.