After a cell synthesizes a protein, the protein folds into its characteristic shape. If a protein is folded wrong, it can no longer perform its job properly. A prion (Table 11.1) is a normally occurring protein produced by brain cells that, when misfolded, causes spongiform encephalopathy.

The term prion is a shortened form of the term proteinaceous infectious particle. Normal prions are present in the brains of all mammals that have been studied. When highly magnified, the normal shape of a prion resembles a coil. The misfolded version of this protein resembles a sheet of paper that has been accordion-folded lengthwise several times when viewed from one end.

The normal role of the prion in the brain is not yet clear, but experiments in mice lacking the prion gene, and therefore unable to make the normal version of the protein, indicate that it may protect mammals against dementia and the other degenerative disorders associated with aging. The very rare CJD seen in elderly people is believed to either arise spontaneously when a prion is mistakenly misfolded or caused by a mutation to the gene that encodes the prion protein in humans, leading to the production of a misfold-ed prion protein.

In contrast, the newly emerging form of the disease that affects younger people, nvCJD, results when an individual is infected by misfolded prion proteins. Remarkably, the misfolded protein searches out properly folded proteins and refolds them into the mutant, disease-causing version. This is very unusual behavior for a protein—no other known protein has this capability.

Over time, the nerve cells in the brain become clogged with the misfolded prions, causing them to improperly transmit normal impulses and eventually cease to function altogether. Ultimately the cells burst, freeing their misfolded prions to find and refold normal prions in other nerve cells. Finally, the brain becomes riddled with empty spaces formerly occupied by normal cells, producing the spongelike character of the diseased brain.

Unlike viruses and bacteria, prions have no RNAor DNA, which were once thought to be necessary for any infectious agent to multiply. Furthermore, although most proteins within cells are easily broken down, prions resist degradation, allowing these rogue disease agents to propagate relentlessly.

All of the infectious agents that had been studied so far had their own genomes, and many researchers did not believe that proteins themselves could be infectious. Dr. Stanley Prusiner, a neurologist at the University of California, San Francisco, was the first to systematically study prions in the early 1980s and the first to link them with disease (Figure 11.5). Although many scientists remained skeptical about his findings, Prusiner was awarded the 1997 Nobel Prize in Medicine or Physiology for his research. However, understanding the nature of prions as infectious agents is only the first step toward preventing spongiform encephalopathies from becoming widespread in humans.

Figure 11.5 Dr. Stanley Prusiner. Dr.

Prusiner, left, won the 1997 Nobel prize for his work with prions.

Figure 11.5 Dr. Stanley Prusiner. Dr.

Prusiner, left, won the 1997 Nobel prize for his work with prions.

Media Activity 11.4 To Vaccinate or Not? What Would Happen if We Stopped?

An epidemic is a contagious disease that spreads rapidly and extensively among a population. An epidemiologist is a scientist who attempts to determine who is prone to a particular disease, where risk of the disease is highest, and when the disease is most likely to occur. Epidemiologists try to answer these questions by determining what the victims of the disease have in common. By identifying what factors increase the risk of a disease, epidemiologists help formulate public health policy. When it is difficult to pinpoint what is causing a disease or how it is spread, deadly epidemics can result (see Essay 11.2). For an epidemic to occur, the infectious agent must cause disease and must be transmissible from one organism to another.

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