Some scientists have found evidence that specific variations in the DNA of mitochondria – structures in cells that provide the energy for cellular activity — can increase the risk of getting PD, while other variations are associated with a lowered risk of the disorder. They also have found that people with Parkinson's disease have more mitochondrial DNA (mtDNA) variations than patients with other movement disorders or Alzheimer's disease. Researchers are working to define how these DNA variations may lead to Parkinson's disease.
In addition to identifying new genes for PD, researchers are trying to learn how known PD genes function and how the gene mutations cause disease. For example, a study found that the normal alpha-synuclein protein may help other proteins that are important for nerve transmission to fold correctly. Other studies have suggested that the normal parkin protein protects neurons from a variety of threats, including alpha-synuclein toxicity and excitotoxicity.
Environmental Impact on Parkinson's
Scientists continue to study environmental toxins such as pesticides and herbicides that can cause PD symptoms in animals. They have found that exposing rodents to the pesticide rotenone and several other agricultural chemicals can cause cellular and behavioral changes that mimic those seen in Parkinson's disease.
Other studies have suggested that prenatal exposure to certain toxins can increase susceptibility to PD in adulthood. An NIH-sponsored program called the Collaborative Centers for Parkinson's Disease Environmental Research (CCPDER) focuses on how occupational exposure to toxins and use of caffeine and other substances may affect the risk of Parkinson's.
Protein Disposal System
Another major area of PD research involves the cell's protein disposal system, called the ubiquitin-proteasome system. If this disposal system fails to work correctly, toxins and other substances may build up to harmful levels, leading to cell death. The ubiquitin-proteasome system requires interactions between several proteins, including parkin and UCH-L1. Therefore, disruption of the ubiquitin-proteasome system may partially explain how mutations in these genes cause Parkinson's.