Parkinsons disease Flashcards
How many people over 65 are affected by Parkinsons?
3-5%
what are the clinical symptoms of parkinsons?
- difficulty in initiating voluntary movement
- shuffling gait
- resting tremor
- rigidity
what gives rise to Parkinson’s symptoms?
- Loss of dopaminergic neurones in the substantia nigra
what are the two main possible causes of parkinsons?
genetic
sporadic
what are the 4 sporadic causes of parkinsons?
- unknown cause
- drug abuse MPTP
- Chemical exposure pesticides
- Personality type
name the 4 genetic causes of Parkinsons?
- DJ-1 (autosomal recessive)
- PINK-1 (autosomal recessive)
- Parkin autosomal rec (juvenile onset)
- Synuclein mutations (juvenile onset)
what does DJ-1 gene do?
protects against free radical production
where does PINK1 gene act?
localised to mitochondria
what does MPTP do?
inhibits mitochondrial complex 1
how was chemical exposure via pesticides studied?
via epidemiological studies - studying farming communities as well as drosophilia models
what does free radical production cause?
oxidative stress
what is parkin?
an E3 ubiquitin-prn ligase
what happens to UPS activity as we age?
it declines
Due to UPS activity decreasing as we age what could this pre-dispose some people to?
Name 5 steps of parkinson’s mechanism?
1) pertubed mitochondrial function -> free radical production -> oxidative stress
2) reduced capacity of UPS -> inadequate clearance of misfolded prns -> accumulation of misfolded prns
3) increased aggregation of alpha-syn -> filaments -> space occupying lesions
4) disruption of vesicular transport
5) prion like spread of alpha-syn oligomers
