Parkinson's Disease - Introduction

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The Mitochondria and Oxygen-Free Radicals. Some research has observed that certain patients with PD have significantly low levels of complex I, an enzyme found in the mitochondria, sausage-like structures that are the primary source of energy within cells. Some theories suggest that low amounts of complex I may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxidants are unstable molecules that bind to other molecules in the body. They are normally produced by the natural chemical processes in the body. If the body is subjected to environmental stresses, however, they can be over-produced. And, in excess, they can damage any cell, including nerve cells in the brain, and even interferes with their DNA.

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NMDA Receptors. Also of interest in PD are processes that occur in an area of the brain called the subthalamic nucleus. Here, receptors known as glutamatergic N-methyl-D-aspartate (NMDA) become persistently overexcited and produce high levels of calcium ions within brain cells. This in turn leads to a cascade of events that trigger oxygen-free radicals and cell damage.

Immune Factors and the Inflammatory Response. An over-responsive immune system triggered by initial damage may also play a role in perpetuating Parkinson's disease. When the immune system becomes overactive, it produces excessive numbers of potent factors called cytokines, which cause inflammation and further injury in brain cells. Important cytokines under investigation are interleukin-1 and tumor necrosis factor.

Genetic Factors

Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Research from the last several years suggests that multiple genetic factors may also be involved in late-onset Parkinson’s disease. Several important studies, published in 2005, lay the groundwork for potential genetic screening for this disease. Researchers identified the leukine-rich repeat kinase 2 (LRRK2) gene, located on a region of chromosome 12 known as PARK8, as a key gene involved in inherited forms of Parkinson’s. The researchers estimate that a single gene mutation in LRRK2 may be responsible for 5% of inherited Parkinson’s cases and approximately 2% of isolated cases.

Early Onset PD. The cases of genetic early-onset Parkinson's disease have most often been detected in specific family groups.