Heredity, or genetic predisposition, may play a role in developing PD. Between 15% and 25% of people with PD report that another relative also has PD. In about 1% of families, PD is known to occur in many members over several generations. Studies of the genetics of these families have identified specific, mutated genes that are linked to PD. However, the results cannot be generalized to all people with PD. Genes are the basis for heredity.
A gene consists of a long strand of four molecules (DNA) arranged like beads on the 23 pairs of chromosomes found in each of us. Each chromosome carries thousands of genes and each gene consists of thousands of molecules of DNA. Genes determine the way in which proteins, the “building blocks” of your body, are made. Hence, if a gene is abnormal, the protein it encodes will be abnormal, and some of these abnormal proteins may cause PD. So far, scientists have identified several mutations and several different locations in humans that are involved in PD. But there is much more to learn. One of the first genes associated with PD, called alpha synuclein (also called Parkin 1), has been identified on chromosome 4 and is responsible for a relatively rare inherited form of PD.
Alpha synuclein is found in Lewy bodies. It appears that the gene mutation involved in the production of alpha synuclein may start a biochemical cascade of events that eventually kills the cell. If the biochemical cascade leading to cell death, called apoptosis, can be interrupted by finding the right drug, a cure may be found. A second gene, which is on chromosome 6, was found by Japanese researchers and is named the Parkin 2 gene. The Parkin 2 gene is found within the nucleus of cells and plays a role in “digesting” proteins. It appears that Parkin 2 gene essentially destroys defective or old proteins. If the Parkin 2 gene itself is defective, the process of destruction is slowed and the defective proteins increase, becoming toxic to the cell by oxidiz-ing and releasing toxic free radicals, which damage the cell or the DNA contained within the cell.
Researchers feel that interplay between several genes and several environmental toxins may be responsible for PD. Genes encode proteins and, ultimately, proteins and how they interact with the environment are a major determinant of many diseases, including PD. An abnormally mutated protein is one factor that deter-mines how that particular protein interacts with the internal and external environment of the cell.
Although at present abnormal genes are the sole cause of PD in only one percent of patients with PD, it’s anticipated that as our understanding of genetics grows, more abnormal genes, such as the LRRK 2 gene found in up to 5% of all patients with PD, including those without a family history of PD, will be found. Much attention is focused on the LRRK 2 gene because it appears in adults, not adolescents, with PD and of the interactions of the protein encoded by the LRRK 2 gene with environmental factors as a cause of PD.