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Deep in the brain, below the cerebral cortex, there are interconnected areas of grey matter collectively known as the basal ganglia (literally "basement structures"). These structures include the caudate nucleus, putamen, and globus pallidus which are involved in controlling voluntary movement. The nerve cells in the substantia nigra (a cluster of cells located next to the basal ganglia) produce dopamine, an essential neurotransmitter which is responsible for transmitting electrical signals between nerve cells. The substantia nigra sends out fibers to the corpus striatum (grey and white bands of tissue in the caudate nucleus and putamen) where the dopamine is released. The transmission of dopamine and its release into the corpus striatum is necessary for smooth, coordinated muscle movement.

Parkinson's disease occurs when there is a disruption of dopamine production which affects neurotransmission (communication between brain cells) in the basal ganglia. If there is a reduction of dopamine levels in the corpus striatum, the nerve cells fire out of control causing a loss of smooth, controlled muscle activity. The death of dopamine-producing cells in the substantia nigra, resulting in a reduced level of dopamine in the corpus striatum, is the primary factor in Parkinson's disease. By the time symptoms develop, there is at least a 60% loss of dopamine-producing cells in the substantia nigra and an 80-90% loss of dopamine in the corpus striatum.

Parkinson's disease is also characterized by the presence of Lewy bodies which are structures found in the cells of the substantia nigra as well as in other secondary locations. Lewy bodies are strongly correlated with neurodegeneration and are considered a diagnostic hallmark of Parkinson's disease.