Other Parkinson's disease studies focus on how Lewy bodies form and what role they play in PD. Some studies suggest that Lewy bodies are a byproduct of degenerative processes within neurons, while others indicate that Lewy bodies are a protective mechanism by which neurons lock away abnormal molecules that might otherwise be harmful. Additional studies have found that alpha-synuclein clumps alter gene expression and bind to vesicles within the cell in ways that could be harmful.
Another common topic of PD research is excitotoxicity – overstimulation of nerve cells that leads to cell damage or death. In excitotoxicity, the brain becomes oversensitized to the neurotransmitter glutamate, which increases activity in the brain. The dopamine deficiency in PD causes overactivity of neurons in the subthalamic nucleus, which may lead to excitotoxic damage there and in other parts of the brain. Researchers also have found that dysfunction of the cells' mitochondria can make dopamine-producing neurons vulnerable to glutamate.
Other researchers are focusing on how inflammation may affect PD. Inflammation is common to a variety of neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, HIV-1-associated dementia, and amyotrophic lateral sclerosis. Several studies have shown that inflammation-promoting molecules increase cell death after treatment with the toxin MPTP. Inhibiting the inflammation with drugs or by genetic engineering prevented some of the neuronal degeneration in these studies.
Other research has shown that dopamine neurons in brains from patients with Parkinson's have higher levels of an inflammatory enzyme called COX-2 than those of people without PD. Inhibiting COX-2 doubled the number of neurons that survived in a mouse model for PD.