We now know that one of the main causes of neurodegeneration is the aggregation of unfolded or misfolded proteins. In the previous article of this series, we have seen that there are characteristic protein aggregates behind different neurodegenerative diseases. In this article, we shall understand a little bit more about Parkinson’s disease –– what kind of neurons get degenerated i.e., damaged and lost, what kind of symptoms characterize the disease, and the existing treatment. 

What is Parkinson’s disease?

Parkinson’s disease is a neurodegenerative disease in which a set of neurons called dopaminergic neurons are lost or damaged. It affects more than 10 million people worldwide and is the second most prevalent neurodegenerative disease after Alzheimer’s disease. The disease is named after James Parkinson, the English doctor who first published a detailed description of the disease. The disease can be familial. That is, a mutation in the gene which carries the message for the synthesis of the ‘alpha-synuclein’ protein is passed on from the parent to the child. It can also be sporadic, caused by factors other than the mutations in genes.

What kind of neurons get degenerated in Parkinson’s disease?

Sections of the brain containing dopaminergic neurons.

‘Dopaminergic neurons’. These neurons produce and release dopamine, a neurotransmitter that plays an important role in controlling body movement, mood, pleasure, reward, etc. These neurons thereby control voluntary movement like the movement of hands, legs, tongue, and also our behaviour like mood, reward, addiction, stress. They are located in three major areas of the brain: substantia nigra, ventral tegmental area (VTA), and the hypothalamus.

Just like wires carrying electricity run through the house from their source to the points where electrical appliances like a fan or a bulb are placed, dopaminergic neurons run from these areas of the brain to other regions where they release dopamine. Based on their route i.e., where these neurons lie and to which part of the brain they release dopamine, these neurons control different functions of the body.

Dopaminergic neurons release less dopamine in patients suffering from Parkinson’s disease.

In Parkinson’s disease, mainly the dopaminergic neurons present in the substantia nigra and VTA degenerate. Also, the neurons in the substantia nigra region are more vulnerable to damage and loss than those in the VTA. Scientists across the world are still trying to understand why this is so. Normally, the dopaminergic neurons in substantia nigra produce dopamine and release them to another part of the brain, called dorsal striatum. In Parkinson’s disease, these neurons get degenerated and the release of dopamine is therefore affected. 

Characteristic features and symptoms

The dopaminergic neurons get degenerated as the misfolded protein, ‘alpha-synuclein’, aggregates in them. These aggregates form structures called Lewy bodies, which damage the neurons. Lewy bodies are also named after Friedrich Lewy, a German neurologist who first discovered abnormal protein deposits in the brains of Parkinson’s disease patients after their death.

However, these changes occur at microscopic levels and cannot be seen through the naked eye. It takes years for these changes to be seen as symptoms in a person. The symptoms are very mild in the beginning and become noticeable only when the disease progresses through the different stages.

Symptoms of patients suffering from Parkinson’s disease.

Stage 1: The person has mild symptoms which do not affect their daily activities. There are some changes in posture, walking, and facial expressions. 

Stage 2: The person experiences tremors and has slight difficulty in walking. Sometimes the person has speech difficulties, like slow speech or slurred speech.

Stage 3: The person loses balance and their movements become slow. At this stage, daily activities like dressing and eating are affected. 

Stage 4: Symptoms become severe and it becomes difficult for the person to walk without a walker and would need help with daily activities. 

Stage 5: This is the most advanced stage. The patient’s legs become stiff, which makes standing and walking impossible. The patient has to rely on a wheelchair or becomes bedridden, and needs someone to nurse. At this stage, one could also experience hallucinations.

While these stages elaborate on the difficulties in movement, which are the major symptoms, there are also symptoms that are not related to movement. These include apathy, depression, memory loss, sleep disorder, and loss of smell and taste.

Treatment

There is no cure for the disease, but the symptoms can be treated. Doctors also advise lifestyle changes, exercises to improve balance, and speech therapy to improve speech problems. The treatment mainly includes dopamine medications that provide dopamine for the brain. ‘Levodopa’, a natural drug that passes into the brain and gets converted to dopamine, is the most commonly used medication. In the early stages of Parkinson’s disease, doctors also prescribe drugs that can prevent the breakdown of dopamine already present in the brain. Such breakdowns are facilitated by a particular enzyme called ‘monoamine oxidase’, and the drug blocks this enzyme.

Treatment options for patients suffering from Parkinson’s disease.

As the disease progresses, however, the medications become less consistent. If the patients are in an advanced stage and experience tremors that cannot be controlled by the drugs, doctors perform a surgical procedure called deep brain stimulation. Surgeons implant electrodes into the specific part of the brain and send electrical pulses which help in reducing the symptoms.

Summary

Parkinson’s disease is caused by the loss of dopaminergic neurons in substantia nigra, a part of the brain. This mainly affects the person’s movement, but there are also other symptoms like loss of smell and taste, apathy, depression, etc. Although there is no cure, the symptoms can be treated. Scientists around the world have been trying to understand the cause and the progression of the disease. This knowledge could enable them to design and develop better treatment measures.

This article is a part of the series on Neurodegeneration. Find the rest of the articles from this series here.

Illustrator: Leeba Ann Chacko

Edited by: দেবদত্ত পাল। Debdutta Paul