Parkinson's Disease Flashcards
What is parkinson’s disease
A neurodegenerative movement disorder that occurs predominantly of old age
Who is Parkinson’s disease most likely to target
Disease occurs in age 65 or over more commonly
More common in men than women
What is parkinson disease typically presented as
Resting tremor
Akinesia: loss of movement: random freezes
Bradykinesia: slow movement
Dementia in later stages: memory problems
Psychiatric symptoms: depression and anxiety
What is the epidemiology of parkinsons disease
8.9 to 19 per 100,000 in developed world
1-2% population over 65 have parkinson’s disease
What is the leading cause of death in parkinsons disease
Incapacitation: unable to function leaves you with opportunistic infection such as pneumonia
What is the pathology of parkinsons disease
Loss of neurons that are predominantly dopaminergic and in the substantia nigra
Accumulation of intracellular inclusions such as Lewy Bodies made up of protein alpha synuclein
Lewy bodies: lumps of sticky proteins
How does neuronal loss occur in parkinson’s disease
Basal ganglia in the middle of the brain
Marked change in coloration of substantia nigra (dark substance): melanin found in skin
Lewy bodies fill up remaining cells and prevent them from working: kill cells and lead to cell death
Death of substantia nigra leads to information being reduced and impairs travelling through cortex (cascade signals reduced)
What does depletion of dopamine lead to in parkinson’s disease
Leads to symptoms such as tremor, slowed movement
It is a necessary neurotransmitter in the substantia nigra
Basal ganglia has reduced amount of dopamine
Give examples of how brain cell die in parkinson’s disease
Genetic component
Environmental issue: Pesticide exposure and MPTP exposure
Related exposure to influenza and repeated head trauma
What is MPTP
Synthetic heroin
Becomes MPP+ when it crosses the BBB and enters via mitochondria
Shutdown starves substantia nigra causing it to die off
What is familial parkinsons disease dependent on
Several loci identified: both recessive and dominant inheritance
Dependent on phenotypes and proteins
Example: LRRK2, SNCA/MAPT: cause brain to partly die
Explain the pathways to neuronal death
Damage to mitochondria via substances like MPP+
Oxidative stress
Ageing
Pesticides
Damage and repair
What is protein aggregation
- Mutations in alpha synuclein linked to familial parkinsons disease: realisation that lewy bodies made this protein up
- Alpha synuclein: readily aggregates, forms toxic lumps of sticky protein amyloid, similar to those found in alzheimer’s
- Hypothesis: aggregates of synuclein oligomers can spread cell to cell and cause cell death
How is dopamine synthesised
L-Tyrosine becomes L-Dopa (tyrosine hydroxylase)
L-Dopa becomes Dopamine (Dopa decarboxylase)
Dopamine becomes norepinephrine
Describe L-Dopa use, where it is converted and how to prevent this
- Natural precursor that can cross BBB- becomes dopamine once in the brain, replaces dopamine to treat symptoms
- 90% of L-dopa is converted in intestinal wall
Prevented using DDC inhibitors CARBIDOPA or BENSERAZIDE - 5% of L-DOPA is metabolised by plasma catechol O methyl transferase. COMT inhibitor ENTACARPONE can be used as adjunct
