L-Dopa (Levodopa): a drug that is converted by nerve cells into dopamine. (Dorsey, 160 An amino acid “precursor” of dopamine and… and a commonly used drug in the treatment of Parkinson disease. (PubMed Health1) Initially, L-dopa was viewed as a cure, but after a honeymoon of several years, it fell out of favor because it was only effective as long as there were dopamine-producing cells in the “substantia nigra.” It turned out that as more dopamine-producing cells died, the drug’s beneficial effects wore off abruptly, leaving patients with involuntary movements. (Kandel4, 163)

Lewy Bodies: aggregates of protein inside the nerve cells, mostly in the “brain stem” and “basal ganglia” but also in the “visual association cortex.” (Sacks, 140) Inclusions, or clumps of proteins (found inside certain neurons in the brains of people who had died of Parkinson’s disease. First described by Frederick Lewy in 1912, they are a hallmark of the disease. The Lewy bodies inside dopamine-producing neurons are clumps of misfolded proteins that are thought to kill the cells. (Kandel4, 161-162) Dr. Lewy, a Jewish neurologist who later fled Nazi Germany… examined the brains of deceased individuals who had had Parkinson’s. He was the first to observe clusters of the misfolded protein. Present in almost all cases, Lewy bodies are now considered to be landmarks of the disease. (Dorsey, 24)

Parkinsonism: any syndrome that results in a combination of tremors, slow movements, rigidity, and imbalance. Has many causes, including (the chemical) MPTP, some antipsychotic medications, infections, and neurological diseases. Parkinson’s disease is the most common cause of Parkinsonism. (Dorsey, 19)

MPP+: toxic (compound) found In the brain produced by the chemical ‘MPTP.’ It’s chemical structure is remarkably similar to a pesticide called ‘paraquat.’ (Dorsey, 24). It kills nerve cells in the substantia nigra— the cells that die off in Parkinson’s. (Dorsey, 19) Additional chemicals linked to Parkinson’s include the pesticide ‘rotenone’ as well as ‘Agent Orange’ which eviscerated the jungles of Vietnam during the war in that country. (Dorsey, 22) Dr. William Langston and Dr. Caroline Tanner found that farmers who used paraquat and rotenone, were more than twice as likely to develop Parkinson’s as those who did not. The results suggested that chronic exposure to certain pesticides could indeed lead to Parkinson’s years or decades later. (Dorsey, 23)

Parkinsons Impact: over the last twenty-five years, Parkinson’s disease is the only neurological disorder (with) deaths, disability, and number affected… increasing, even after adjusting for age. (Dorsey, 34) About 1 million people in the United States have Parkinson’s disease. Every year, sixty thousand new cases are detected and a significant number of additional cases evade detection. Usually begins around the age of sixty. (Kandel4,161) Parkinson’s affects more than just dopamine-producing nerve cells in the substratia nigra. Other regions of the brain producing different neurotransmitters also suffer cell loss. This additional damage is responsible for many of the symptoms of Parkinson’s that are not related to movement or motor function, such as disturbed sleep, anxiety, pain, and thinking difficulties. (Dorsey, 16) Perhaps a third or more of those being treated for Parkinson’s experience “hallucinations.” People with Parkinson’s may sleep poorly at night and often have chronic “sleep deprivation.” People with ordinary Parkinson’s disease do not usually experience visual hallucinations until they have been on medication for many months or years. (They) may be active and retain their intellectual powers for decades. (Sacks6, 124) For those that develop Parkinson’s before (age) fifty, genetic factors appear to be more important. The younger the age at onset, the greater the likelihood that genetics play a role. Today, about 10% of people living with Parkison’s are thought to have an underlying genetic cause as the principal explanation for their disease. According to Dr. Caroline Tanner, “for people with Parkinson’s disease diagnosed after age 50, it’s most commonly caused by environmental factors.” (Dorsey, 27)

Parkinsons History: first described in 1817 by the British physician James Parkinson in his ‘Essay on the Shaking Palsy.’ Parkinson described three characteristics: tremor at rest, abnormal posture, and slowness and paucity of movement. In 1919, Konstantin Tretiakoff, a Russian medical student, described the substantia nigra, as a part of the brain that he thought was involved in Parkinson’s disease. (Kandel4,161) Researchers found that levels of dopamine in the brains of people who had had Parkinson’s were ten times lower than in those without the condition. The lower the dopamine levels, the worse the symptoms. (Dorsey, 16) Arvid Carlsson (discovered) that Parkinson's Disease may result from a lowered concentration of dopamine in regions of the brain that are involved in motor control. He and others tested this idea and found that they could reverse the symptoms by giving patients additional dopamine. (Kandel, 356) Subsequent studies by Carlsson showed that dopamine is essential to the regulation of muscle movement. (He) went on to find that the early symptoms of Parkinson’s disease result from the death of dopamine-producing neurons in the substantia nigra. Today, we know that those neurons die from a protein-folding disorder. As the disease worsens, other areas on the brain besides the substantia nigra become involved. Oleh Hornykiewicz of Austria found at autopsy that dopamine is depleted in the brain of people with Parkinson’s. In 1967, George Cotzias gave patients L-dopa to replace the depleted dopamine. (Kandel4,162-163) In 1997, Dr. Mihael Polymeropoulos from the NIH and his colleagues identified a mutation in the alpha-synuculein gene in a large Italian family and three Greek families with Parkinson’s Disease. The gene gives instructions for the building of alpha-synuclein protein. This protein helps move neurotransmitters within nerve cells. The mutation caused the proteins to misfold. (Dorsey, 23-24)