Parkinson’s disease (PD) is progressive nervous system disorder, and is the second most common neurodegenerative disorder behind Alzheimer’s disease. Additionally, PD affects patients by impairing the parts of the brain responsible for movement, and leads to the observed motor deficiencies.1 Parkinson’s disease was first identified in 1817 by James Parkinson. He looked into six patient case studies and determined a few of the major symptoms, and some initial ideas for treatment options in the future.2 Over the course of the next 200 years, more of the symptoms were determined by researchers like Charcot and Brissaud, and methods of diagnosis were improved.3,45
The main symptoms associated with Parkinson’s are bradykinesia (slowness of movement), dyskinesia (impairment of voluntary movement), tremor at rest, muscular rigidity, postural instability, loss of automatic movements, as well as many other less common movement impairments.13 The cause of these movement impairments is due to neuron damage in the brain. The area of the brain that is tied to Parkinson’s disease is the substantia nigra (meaning dark substance because of its dark pigmentation), which is a part of the brain that makes up the midbrain and the basal ganglia (section that is in the center of brain and connects to the spinal cord). One piece of the substantia nigra, the pars compacta, is heavily involved in the signaling pathway responsible for movement. The pars compacta is made up of dopamine producing neurons called dopaminergic neurons.19When movement signaling occurs, the dopaminergic neurons release dopamine to another section of the brain involved in movement, called the striatum. When this pathway is completely active, proper movement can occur. However, in the case of Parkinson’s disease, growths are able to develop within the dopaminergic neurons, and disrupt function or even kill the neuron. Because the dopaminergic neurons are dying, no dopamine is produced and transmitted to the striatum. This results in improper movement signaling, and the observable PD symptoms like tremor or rigidity.12
Although this process may seem somewhat straightforward, the method in which the Lewy bodies begin to form and subsequently destroy neurons, is unknown. It is known however, that a particular protein that is expressed in the brain, called alpha-synuclein.22Studies have indicated that a significant amount of aggregated alpha-synuclein makes up a large portion of lewy bodies.23The protein alpha-synuclein resides on the edges of neurons called presynaspes, and its normal job is to facilitate releasing cellular products so that they can travel to other neurons in the brain, and continue on pathway signaling. Its normal shape is a long strand, with a curled section of alpha-helices on one end.24 By some sort of disease causing mechanism that remains uknown, the alpha-synuclein will abandon its regular shape, and misfold into a new one. After misfolding, multiple individual misfolded alpha-synucleins will come together and make a larger structure, called an oligomer. The oligomer will continue elongating until a fibril is formed. The fibril form of alpha-synuclein is what makes up the destructive Lewy bodies, and is what is toxic to the neurons.33
Researchers do not know precisely what causes the alpha-synuclein to begin misfolding. However, they do know that there are more than 20 genes that have Parkinson-causing mutations. Each mutation initiates familial (genetic) Parkinson’s in a different way, and differently from the more common idiopathic (non-genetic) PD.9 One example of a gene, which was actually first identified PD-assoicated gene, is SNCA. The SNCA gene is responsible for alpha-synuclein being created. When there is a mutation in SNCA, the typical shape of the protein is unusual, and typically results in more common aggregation, and subsequent Parkinson’s disease progression.7
In terms of treatment for PD, there is none that is completely consistent and no definitive cure. Because we don’t have a complete understanding of the biochemistry involved in Parkinson’s disease, we have no way to directly target alpha-synuclein or Lewy bodies. As a result, most of the treatments that are used today are used in order to lessen symptoms. An example is levodopa. Levodopa, when ingested, is able to be converted into dopamine and transferred into the brain.42This is extremely useful in replacing the lost dopamine due to neuronal death. Hopefully as more and more of the science of Parkinson’s is understood, we can get closer to finding a cure for this debilitating disease.