Lecture 25 Flashcards
What are the key symptoms of parkinsons disease?
Tremor
Muscular rigidity
Bradykinesia
What are the 2 categories of parkinsons disease?
Parkinsonian syndromes
Symptomatic parkinsonism
What are the pathological amd biochemical findings in parkinsons disease?
Lesions of the basal ganglia particularly in the substantia nigra
Nigrostriatal pathway affected
What do the basal ganglia control?
Movement possible initiation
What does astrogliosis cause?
Scar formation and can sometimes inhibit axon regeneration
What are the g alpha s coupled dopamine receptors?
D1 and D5
What are the G alpha i coupled dopamine receptors?
d2, d3 and d4
What is observed in the histopathology of parkinsons?
Lewy bodies
Cell loss
What are lewy bodies?
Proteinaceous lumps in the cytoplasm containing: lipids, alpha synuclein, ubiquitin, neurofilament and symphilin 1
What mutation in familial parkinsons affects alpha synuclein?
SNCA
What mutation in familial parkinson’s affects E3 ubiquitin ligase?
PARK2
What are the physiological roles of alpha synuclein?
Activity dependent regulation of dopaminergic neurons or regulation of synaptic vesicle pools
Co-chaperone of proteins that protect nerve terminals against injury
Trafficking of cargo in the ER
What is the link between alpha synuclein and parkinsons?
It is prominent in lewy bodies, an autosomal domiannt mutation in familial pd and processed by the ubiquitin proteasomal pathway
What is the average rate of cell loss from the substantia nigra?
5% a decade
What is the frontline treatment for parkinsons?
L-DOPA
What are the problems with L-DOPA?
95% used in peripheral tissue
Unwanted side effects include nausea, involuntary choreiform movements
Use is time limited as patients develop on/off behaviour then no response at all
How can you optimize L-DOPA usage?
Inhibit DOPA decadboxylase
Inhibitiion of DA degradation via MAO or COMT
Block of peripheral DA receptors
Delay use of L-DOPA
Give an example of a drug that inhibits monoamine oxidase in the CNS
Selegitine
Give an example of a drug that inhibits catechol-o-methyl transferase
Entacapase
Give an example of a drug that blocks peripheral DA receptors
Domiperidine
Other than L-DOPA how can you treat Pd?
Drugs that mimic the action of DA
Drugs that reduce DA metabolism
Surgery
Give an example of a drug that mimics the action of DA
Bromicriptal lisuride
Give us an example of an mao-b inhibitor that can be used in pd treatment
Selegitine
Give an example of a COMT inhibitor that can be used to treat pd
Entacapase
Who first described parkinsons disease and when?
James Parkinson in 1817
