Misfolded Proteins and Neurodegenerative Diseases
Accumulation of misfolded proteins can cause disease, and unfortunately some of these diseases, known as amyloid diseases, are very common. The most prevalent one is Alzheimer's disease, which affects about 10 percent of the adult population over sixty-five years old in North America. Parkinson's disease and Huntington's disease have similar amyloid origins. These diseases can be sporadic (occurring without any family history) or familial (inherited). Regardless of the type, the risk of getting any of these diseases increases dramatically with age. The mechanistic explanation for this correlation is that as we age (or as a result of mutations), the delicate balance of the synthesis, folding, and degradation of proteins is perturbed, resulting in the production and accumulation of misfolded proteins that form aggregates (Figure 4; Finkel 2005).
Among the environmental factors known to increase the risk of suffering degenerative diseases is exposure to substances that affect the mitochondria, increasing the amount of oxidative damage to proteins. However, it is clear that no single environmental factor determines the onset of these disorders. In addition, there are genetic factors. For example, in the simplest forms of familial Parkinson's disease, mutations are associated with dominant forms of the disease. This means that an individual with a single copy of a defective gene will develop the disease, yet two copies of the defective gene are required for recessive forms of the disease to develop. In the case of Alzheimer's disease, and for other less common neurodegenerative diseases, the genetics can be even more complicated, since different mutations of the same gene and combinations of these mutations may differently affect disease risk (Dobson 2002, 2003; Chiti & Dobson 2006).