Overview of Parkinson’s Disease

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

Brief timeline of the history of Parkinson’s disease over the past 200 years. Created using Adobe Spark.

            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.


Parkinson’s Disease Pages – Table of Contents

6 replies on “Overview of Parkinson’s Disease”

With Parkinsons, do all of your Alpha-Synuclein proteins change their shapes to link with others, or only some of them?

Thank you for the question! The amount of alpha-synuclein that has misfiled and formed aggregates depends on how far along the disease has progressed. At the onset of the disease, there is a very low level of aggregated alpha-sun. However, as the disease progresses and symptoms become more apparent, there is more and more protein aggregation.

Hey Matt. I have read about Levodopa (L-DOPA) before. I understand that it serves as a precursor for neurotransmitters like dopamine. Thus it makes total sense to use Levodopa to treat PD. There is another way to produce ‘more’ dopamine through the use of dopamine agonists. I’m going to make the assumption that dopamine agonists have been used to treat PD. I’m curious to understand the efficacy of these two treatments. Would one work better than the other, and if so why?

Hi Sam, thanks for the question! There is further information regarding treatment options for Parkinson’s disease which is located on my treatments page that is linked above. In terms of efficacy, L-DOPA is by far the most effective, but the negative implications that may go along with them is a concern. As a result, L-DOPA is typically not the first treatment that is applied, rather it is used when PD symptoms have progressed significantly, and in an attempt to live life as normally as possible, levodopa is used to combat the severe motor dysfunctions. Dopamine agonists, although less effective, are still valuable in treatment of this disease and are used prior to severe symptoms.

Although not a cure, when Levodopa is used and converted to dopamine will it help patients with their motor skills and can it be used long term?

You are absolutely correct in this question! The main reason that levodopa is used in treating Parkinson’s is not to ‘cure’ the disease, but rather to tend to the life-altering motor symptoms associated with them. As the dopamine producing cells begin to die in the regions of the brain responsible for movement, proper motor function takes a hit. However, if you supplement this area with dopamine by introducing levodopa, you can effectively replace the dopamine that is no longer being produced. In terms of timing with this treatment, levodopa is often used when symptoms have progressed significantly. As a result, levodopa is typically used as a treatment for the remainder of the patient’s life in an attempt to have their life remain as normal as possible.

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