How Parkinson's disease spreads in the Brain?

Table of Content

• What is Parkinson’s disease?

• How does Parkinson's disease affect the brain?

• Spread of Parkinson's Disease in the Brain

• Tracking the spread of Parkinson's proteins from the gut to the brain

• Parkinson's disease treatment

• Take-Home Points

• FAQs on How Parkinson's disease spreads in the Brain?

Introduction 

Parkinson’s Disease is a movement disorder in which a person experiences tremors, rigidity of limbs, postural instability and other symptoms.

Parkinson's disease affects the substantia nigra(part of the brain) which is responsible for the production of dopamine. This is the reason that Parkinson’s disease is not just limited to movement but it also affects mood and behaviour.

In this blog, we’ll focus on the Spread of Parkinson's disease in the brain, how Parkinson's disease affects the brain, Parkinson's disease treatment etc.

What is Parkinson’s disease?

Parkinson’s disease is a movement disorder which progresses with time as the neurons die or get damaged. People experience tremors, rigidity, slow movement, even expressionless faces and slurred speech in later stages.

Parkinson’s disease is caused by to deposition of alpha-synuclein protein in the form of Lewy bodies. There is no complete cure for Parkinson's disease but treatment outcomes are quite well

The four characteristic symptoms of Parkinson’s disease are:

1. Tremors: Tremors or shaking in Parkinson’s disease often appear on one side, it is commonly seen in hands but sometimes the foot or jaw can be affected. Tremors in hands are usually seen as the person is rolling a pin characteristically called a ‘‘Pin rolling tremor’’. Tremors disappear when a person does some intentional activity with their hands or if a person sleeps.

2. Rigidity: Rigidity means stiffness of muscles. Stiffness of muscle can be felt on someone else tries to move the limbs and experiences resistance. Rigidity in Parkinson's disease is of Cogwheel type meaning there are jerky movements in between the rigidity.

3. Bradykinesia: Bradykinesia refers to slowed movement, it takes more time for the person to perform simple tasks which were earlier done easily. There are masked faces which means expressionless faces.

4. Postural instability: Postural instability appears quite late in Parkinson's disease. A person finds difficulty maintaining balance and posture.

Other symptoms associated with Parkinson's disease are:

1. Depression

2. Sleep problems

3. Urinary problems

4. Emotional changes

5. Easy fatigability

6. Dementia 

How does Parkinson's disease affect the brain?

Parkinson's disease is characterized by the deposition of abnormal proteins called Lewy bodies in brain cells, these Lewy bodies are made up of alpha-synuclein. 

Due to the deposition of these in the brain cells, communication between the cells gets disrupted. Classical features of Parkinson’s disease occur when these proteins start deposition in Substantia Nigra, which hampers the production of Dopamine. 

Substantia nigra can be thought of as the ‘accelerator of the car’. If it doesn't function properly there is a slowing of movements known as Bradykinesia.

Apart from motor symptoms Parkinson’s disease also affects non-motor symptoms like depression, loss of smell, emotional changes etc. We have discussed them in the above sections.

Spread of Parkinson's Disease in the Brain

Parkinson’s disease starts from a part of the brain substantia nigra pars compacta then subsequently spreads to other parts of the brain. Braak staging is used to understand the spread of Parkinson’s disease in the brain:

Six stages of Braak staging are identified based on the part of the brain affected. Initial symptoms of Parkinson's disease are non-motor-like lessened smell sensation, motor symptoms usually appear in later stages of break staging or mid-stages.

1. Stage 1: Stage 1 begins from the olfactory system and lower brainstem. Loss of smell is observed first. Thread-like alpha-synuclein deposits are seen.

2. Stage 2: In stage 2 disease progresses to structures in the medulla apart from the structures affected in stage 1.

3. Stage 3: In this stage, the Lewy bodies start to deposit in substantia nigra pars compacta and the person starts to have symptoms like tremors, rigidity etc. In the later part of stage 3 Lewy bodies start deposition in the basal nucleus of miners.

4. Stage 4: This stage is characterized by the destruction of dopaminergic neurons. Significant damage is done to the nucleus in the brain which is responsible for smell(olfactory nucleus).

5. Stage 5: Disease starts spreading in the neocortex and spreads in the temporal, parietal and frontal lobes. Cells are dead in the substantia nigra at this stage.

6. Stage 6: Disease completely spreads to the neocortex and both motor and sensory areas of the brain get affected.

Tracking the spread of Parkinson's proteins from the gut to the brain

Recent advances in Parkinson's disease suggest that alpha-synuclein abnormal clusters are found in the gut. Alpha-synuclein deposits have been found in the gut also and Researchers have proposed that alpha-synuclein can first misfold and deposit in the gut then in the Brain.

Recent advances also suggested that misfolded alpha-synuclein can cause nearby normal alpha-synuclein to misfold. This can lead to a chain reaction in which misfolded alpha-synuclein deposits from the vagus nerve to the brain.

Further research has also been performed by researchers to test the idea in mice, and they injected the misfolded alpha-synuclein and they found that it does spread to the brain.

Parkinson's disease treatment

Parkinson's treatment usually involves medication which increases dopamine levels in the brain because the area which is affected is substantia nigra pars compacta which is responsible for the production of dopamine. 

Dopamine levels decrease in Parkinson's disease and contrary to this Acetylcholine levels rise. Most of the medications work on Dopamine and Acetylcholine.

Refractory cases of Parkinson's disease require surgery or Cases which don't respond to medications.

Drugs which are used in the treatment of Parkinson's disease are:

1. Levodopa and Carbidopa: Levodopa is picked up by neurons in the brain to form dopamine. One cannot take dopamine directly as it cannot cross the Blood-brain barrier directly. Levodopa is added with carbidopa so that Levodopa cannot be converted to dopamine apart from the brain. 

2. Anticholinergic drugs: Anticholinergic drugs are advised to reduce symptoms of tremors.

3. MAO-B inhibitors: MAO-B inhibitors inhibit Monoamine oxidase B enzyme which breaks dopamine into inactive form. Drugs include selegiline and rasagiline.

4. Dopamine Agonist: These drugs mimic dopamine and act like dopamine. These can be combined with Levodopa(L-dopa) or can be given alone. They are somewhat less efficient than L-dopa.

5. COMT inhibitors: COMT inhibitors are catechol-O-methyltransferase which is another enzyme apart from MAO-B which breaks dopamine. COMT inhibitors are combined with L-dopa to prolong the action of dopamine. Drugs include entacapone and talcapone.

6. Amantadine: Amantadine is an antiviral which is used in the treatment of Parkinson's disease. This drug is mainly used to treat levodopa-induced dyskinesia symptoms.

Patients who don't respond to treatment or drugs for Parkinson's disease in itself cause Disordered movements they can be suitable for Surgery. Surgeries for Parkinson's disease include:

1. Pallidotomy and Thalamotomy

2. Deep brain stimulation

Take-Home Points

1. Parkinson’s Disease is a movement disorder in which a person experiences tremors, rigidity of limbs, postural instability and other symptoms.

2. Parkinson's disease affects the substantia nigra(part of the brain) which is responsible for the production of dopamine.

3. Parkinson’s disease is caused by to deposition of alpha-synuclein protein in the form of Lewy bodies. 

4. The four characteristic symptoms of Parkinson’s disease are Tremors, rigidity, bradykinesia, and postural instability.

5. Brakk staging is used to stage the spread of Parkinson’s disease in the Brain.

6. Recent advances in Parkinson's disease suggest that alpha-synuclein abnormal clusters are found in the gut.

7. Recent advances also suggested that misfolded alpha-synuclein can cause nearby normal alpha-synuclein misfold.

8. This can lead to a chain reaction in which misfolded alpha-synuclein deposits from the vagus nerve to the brain.

9. First-line treatment for Parkinson’s disease is drugs which include Levodopa, carbidopa, MAO-B inhibitors, COMT inhibitors, Amantadine etc.

10. Refractory cases or People experiencing disordered movement symptoms as a result of taking drugs(drug-induced dyskinesia) require surgery.