- Genetics About 15-25% of Parkinson's patients report having a relative with Parkinson's. Researchers have found a defective gene in some rare families, with a high incidence of Parkinson's disease. These rare cases have an inherited form of Parkinson's disease. Scientists have discovered several "Parkinson's genes" and there is conclusive evidence that genetics play a role in at least some patients. There appears to be a 2-3 fold increased risk of PD in first degree relatives compared to matched control populations. However, the majority of cases of PD still appear to be sporadic.
- Environmental Factors Some scientists have suggested that Parkinson's disease may occur when a toxin selectively destroys dopaminergic neurons. Scientists have known for a number of years of several toxins that can cause Parkinson's-like symptoms, such as MPTP. Several studies have suggested a link between rural living, herbicide use and exposure to pesticides as possible factors that may contribute to a person's developing Parkinson's. Some PWP's recall a time when they were exposed to chemicals, and believe this exposure may be a possible cause. Scientists are continuing to pursue these clues to establish more concrete linkages.
While the debate concerning environmental factors and genetics as causative factors in PD continues, there has been extensive investigation of the mechanisms involved in the cell death process. A number of cell death concepts have been put forward including, oxidative stress, mitochondrial dysfunction and excitotoxicity.
- Oxidative damage This theory suggests that free radicals - unstable molecules whose toxic effects are believed to be caused by oxidation - may contribute to cell death, thereby leading to Parkinson's disease. Oxidation is thought to cause damage to tissues, including neurons. In addition, antioxidant defenses appear to be markedly reduced in PD brains. In particular, reduced levels of glutathione (an acid which plays a role in the detoxification of harmful compounds) have been discovered. The cause of the deficiency and the potential role that antioxidants like glutathione play in the development of PD remain unresolved.
- Mitochondrial dysfunction The mitochondria are small bodies within cells that produce energy. They can be described as the 'power-house' of the cell. Scientific findings indicate a reduction in the function of mitochondria and this may play a role in PD.
- Excitotoxicity occurs when selected neurotransmitters in the brain get out of balance leading to cell death. This mechanism has been documented in Parkinson's and scientists believe that glutamate excitotoxicity is the main culprit within this mechanism. Finding a way to correct this imbalance may prevent be neuroprotective.
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