PD is a neurodegenerative disease. It occurs when certain nerve cells, or neurons, die or become impaired. This degeneration takes place in an area of the brain called the substantia nigra, located in the brainstem, which is one of the centers that control movement (also called the basal ganglia). Normally, these neurons produce a chemical known as dopamine, which is responsible for transmitting signals across the nerve pathways to produce smooth, purposeful movements. Loss of dopamine causes nerve cells to fire abnormally. This leaves people living with PD with difficulty directing or controlling their movements in a natural manner. People living with PD have usually lost 80% or more of dopamine-producing cells in the substantia nigra by the time symptoms are visually apparent. In addition, there is also neuronal cell loss and related pathology in other brain regions, responsible for other non-motor symptoms.
The main reason why these cells die or become impaired is still a mystery. Most scientists believe that both genetic and environmental factors are contributing causes. However, how they lead to PD is still unclear.
Genetics Factors of Parkinson’s Disease
While Parkinson’s disease is not usually inherited, familial forms exist and first-degree relatives of people living with PD are at slightly higher risk for the condition. When a genetic vulnerability is combined with exposure to some –yet unknown- environmental trigger, the changes for developing the disease increase. This genetic contribution appears to be stronger for those cases of early-onset PD.
The study of families in which PD appears to be inherited has resulted in the discovery of several genes associated with PD. There are two types of genes associated with disease. There are “causal genes” in which the causal gene alone, without the influence of other genes of environmental factors, guarantees that a person who inherits will very likely develop PD. This type of genetic PD is very rare. The second type, “associated genes”, do not cause PD on their own, but increase the risk of developing it. These genes usually need to be combined with other genes and environmental factors to cause PD.
At the present time, mutations in at least five genes have been firmly associated with PD: alpha-synuclein (SNCA or PARK1), parkin (PRKN or PARK2), DJ-1 (or PARK7), PTEN-induced putative kinase 1 (PINK1 or PARK6) and leucine-rich repeat kinase 2 (LRRK2 or PARK8). The identification of genes associated with PD has allowed scientists to better understand the disease. At the present time, genetic PD is treated in the same way as non-genetic or sporadic PD and clinical genetic testing is not usually performed. Because of the complexity associated with the genes associated with PD, genetic counseling is always recommended when performing genetic testing.