Parkinsons’s disease and neurodegenerative disorders

Question 1

What is Parkinson’s Disease?

Answer 1

A progressive motor control disorder characterised by tremors and regidity

Question 2

What causes Parkinson’s disease?

Answer 2

A substantial reduction of dopamine in the substantia nigra, affecting the nigrostriatal pathway responsible for voluntary movement

Question 3

How does dopamine loss affect movement?

Answer 3

Dopamie normally inhibitys excitatory acetylcholine transmission, but its depletion leads to excessive acetylcholine-driven excitation, causing motor symptoms

Question 4

What are potential contirbutors to dopaminergic loss in Parkinson’s?

Answer 4

1. Protein Misfolding and aggregation (Lewy bodies, α-synuclein)
2. Excitotoxicity from overactive neurons, leading to cell death
3. Oxidative stress (free radicals from metabolism and inflammation)
4. Apoptosis (programmed cell death)
5. Envrionmental toxins (MPTP exposure from illicit drug syntheis)

Question 5

What are the main tratment approaches for Parkinson’s disease?

Answer 5

1. Replenish dopamine in the substantia nigra
2. Enhance D2 receptor-mediated inhibition
3. Reduce acetylcholine-mediated excitation

Question 6

Why is Levodopa (L-DOPA) the first-line treatment?

Answer 6

Dopamine cannot cross the blood-brain barrier, but L-DOPA enter the brain and is converted to sopamine by DOPA decarboxylase in temaining neurons

Question 7

What limits L-DOPA’s effectiveness?

Answer 7

Only 5-10% reaches the brain, leading to peripheral dopamine acitvity that causes side effects (nausea, dyskinesia, joint stiffness)

Question 8

How do extracerebral decarboxylase inhibitors help?

Answer 8

Carbidopa or benserazide inhibit peripheral decarboxylation of L-DOPA, reducing side effects while allowing conversion to dopamine in the brain

Question 9

What are other drug strategies beyond L-DOPA?

Answer 9

• D2 receptor agonists (e.g., bromocriptine, lysuride) → Enhance inhibition in the pathway.
• Monoamine oxidase-B (MAOB) inhibitors (e.g., selegiline) → Reduce dopamine degradation.
• Muscarinic acetylcholine receptor antagonists (e.g., benzhexol, benztropine) → Reduce acetylcholine-driven excitation.
• Catechol-O-methyltransferase (COMT) inhibitors (e.g., tolcapone) → Prevent peripheral L-DOPA metabolism.

Question 10

What psychological side effects can Parkinson’s treatments cause?

Answer 10

Hallucinations
Psychosis
Confusion from excessive dopaminergic transmission in the mesolimbic system (linked to schizophrenia).

Question 11

What is social prescribing?

Answer 11

Community-based programs supporting patients with neurological and mental health disorders.

Question 12

What are examples of social prescribing initiatives?

Answer 12

Art therapy
Gardening
Singing group
Exercise-based rehabilitation
Elderly lunch clubs

Question 13

Why is social prescribing gaining focus?

Answer 13

Increased mental health challenges and ageing population prompt NHS-funded regional programs to improve patient well-being.

Question 14

What neurodegenerative diseases involve protein aggregation?

Answer 14

Prion diseases (Creutzfeldt-Jakob’s, Kuru, Bovine Spongiform Encephalopathy)

Question 15

What causes Huntington’s disease?

Answer 15

Trinucleotide repeat expansion in the huntingtin gene, leading to toxic polyglutamine accumulation

Question 16

What is multiple sclerosis?

Answer 16

A demyelinating disorder, causing nerve conduction deficits and neuroinflammation

Question 17

What regions are affected in Alzheimer’s disease?

Answer 17

Hippocampus & basal forebrain, causing short-term memory loss and cognitive impairment

Question 18

How is Alzheimer’s treated?

Answer 18

Acetylcholinesterase inhibitors (e.g., donepezil, galantamine, rivastigmine) improve cholinergic transmission but do not halt disease progression