A special class of protein structures, utilized for some normal cell functions, can also contribute to human diseases when not controlled. These are self-propagating, stable β-sheet aggregates called amyloid fibrils. These fibrils are built from a series of identical polypeptide chains that become layered one over the other to create a continuous stack of β sheets, with the β strands oriented perpendicular to the fibril axis to form a cross-beta filament (Figure 3–31). Typically, hundreds of monomers will aggregate to form an unbranched fibrous structure that is several micrometers long and 5 to 15 nm in width. A surprisingly large fraction of proteins have the potential to form such structures, because the short segment of the polypeptide chain that forms the spine of the fibril can have a variety of different sequences and follow one of several different paths (Figure 3–32). However, very few proteins will actually form this structure inside cells.
In normal humans, the quality control mechanisms governing proteins gradually decline with age, occasionally permitting normal proteins to form pathological aggregates. The protein aggregates may be released from dead cells and accumulate as amyloid in the extracellular matrix. In extreme cases, the accumulation of such amyloid fibrils in the cell interior can kill the cells and damage tissues. Because the brain is composed of a highly organized collection of nerve cells that cannot regenerate, the brain is especially vulnerable to this sort of cumulative damage. Thus, although amyloid fibrils may form in different tissues, and are known to cause pathologies in several sites in the body, the most severe amyloid pathologies are neurodegenerative diseases. For example, the abnormal formation of highly stable amyloid fibrils is thought to play a central causative role in both Alzheimer’s and Parkinson’s diseases.
Prion diseases are a special type of these pathologies. They have attained special notoriety because, unlike Parkinson’s or Alzheimer’s, prion diseases can spread from one organism to another, providing that the second organism eats a
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