History and Metabolic Context – Parkinson's

Discovery of Parkinson’s Disease

Dr. James Parkinson, courtesy of google images
Dr. James Parkinson, courtesy of google images

Dr. James Parkinson was born April 11, 1755 in London, England. Throughout his childhood he was surrounded by medicine since his father was a surgeon and James later went on to become a surgeon himself. He had a successful medical career and was very politically active in his time, but by far his most well known contribution to history was his essay describing “shaking palsy” in 1817 which later would be renamed as Parkinson’s disease. Dr. Parkinson wrote about his observations from many different patients he saw that had signs and symptoms of an illness that had not been identified previously. The most characteristic symptom he observed was the tremors and shaking that started out almost unnoticeable and then escalated. He noted that in most patients, it began so gradually and progressed so slowly that the patients could almost never pinpoint the exact time the tremors began. (“Dr. James Parkinson” author not listed)

Signs and Symptoms

Today, Parkinson’s continues to be characterized by tremors, slow movement, and ridigity. Other symptoms of the disease include bladder problems, eye problems, fatigue, speech and communication difficulty, and difficulty swallowing (“Diagnosis”). These are not surprising because Parkinson’s affects the body’s ability to properly move muscles and all of the symptoms are correlated directly with muscular control. This is because the dopaminergic cells in the part of the brain called the substantia nigra are no longer functional and die, making the brain deficient in dopamine.

Diagnosis

The diagnosis for Parkinson’s is complicated because there is no test that can conclusive confirm the presence of Parkinson’s disease in a patient. A physician will conduct a neurologic exam and ask the patient to move to evaluate how the patient is capable of handling simple tasks such as sitting down, standing up, turning around, walking, etc. The examinating physician will look for any signs of tremors or abnormalities in movement, coordination, or balance. Since the defects caused by Parkinson’s are within the neuron itself, MRI or CT scans of a patient’s brain will appear normal even if the patient is showing the symptoms of Parkinson’s (“Diagnosis”).

Disease-Free Biochemical/Cellular Context

Along with other roles, dopamine is a neurotransmitter that allows for movement through a signal transduction pathway that regulates calcium, which is necessary for muscular contractions. One study conducted in 1996  investigated the role dopamine and the dopamine D2 receptor had on calcium ion regulation. The team was able to show that activation of the dopamine D2 receptor decreases intracellular calcium levels, consequently hyperpolarizing the cell and increasing the membrane potential. This makes firing an action potential more difficult and therefore makes the threshold more difficult to reach and the firing of action potentials more deliberate. The D2 receptor works against the D1 receptor which is a G-protein coupled receptor which activates adenylyl cyclase which draws in calcium ions (Lee, A.k.).

 

Diagram of normal cellular responses caused by Dopamine-1-Receptor (D1R) and Dopamine-2-Receptor (D2R) , found on google images
Diagram of normal cellular responses caused by Dopamine-1-Receptor (D1R) and Dopamine-2-Receptor (D2R) , found on google images

This intake of calcium ions is responsible for the release of neurotransmitters from their calcium sensitive vesicle membrane proteins, allowing for the continuation of the synaptic signal. Another component of this pathway is alpha-synuclein, a protein found naturally in presynapse of neurons, however the specific roles of alpha-synculein in the neurons is not yet fully understood. It has been proposed that one role is involved with the regulation of dopamine vesicles being released at the synaptic cleft.

 

Return To Title Page

Molecular Bases of the Disease State

Treatment and Disease Management

Conclusions and Proposals for Future Work