When prions are present in the brain, they replicate by inducing normal prion protein (PrPC) molecules to refold into the abnormal, pathogenic shape. This mechanism is not understood and is the subject of extensive research. The normal prion protein structure is believed to consist of a number of flexible coils called alpha helices. In the abnormal form of the protein, some of these helices are stretched out into flat structures called beta sheets (see Figure 1). The normal protein is broken down by cellular enzymes called proteases but the abnormal protein shape is resistant to these enzymes. As a result, as prions replicate, they are not broken down by proteases and accumulate in brain tissue.
Source: University of Southhampton Environmental Health Unit
The accumulation of prions in the brain causes neuronal cells to die and, in some types of TSE, a type of protein called amyloid accumulates in plaques, or flat areas, and causes degeneration of brain tissue. Recent research suggests prions disrupt the normal cell process of protein recycling which causes a buildup of faulty proteins and causes the death of the cell8. The destruction of neural cells causes tiny holes in the brain tissue and a sponge-like appearance under the microscope, thus giving rise to the term spongiform disease.