parkinsons

Question 1

pathology

Answer 1

loss of dopaminergic neurons and the accumulation of protein aggregates referred to as lewy bodies in the remaining neurons. Dominant mutations in synuclein lead to protein aggregation.

Question 2

what is the leading cause of parkinsons

Answer 2

Dominant mutations in LRKK2 kinase

Question 3

why is lrrk2 an attractive drug target

Answer 3

because it is a kinase

Question 4

what mutation consistently results in increased kinase activity

Answer 4

G20195

Question 5

what causes autosomal recessive forms of PD

Answer 5

homozygous or compound heterozygous mutations in pink1, parkin and park7

Question 6

are there A typical clinical features with mutations in pink1, parkin and park7?

Answer 6

no

Question 7

out of pink1, parkin and park7, which loci is the most common?

Answer 7

parkin

Question 8

what type of mutation is LRKK2

Answer 8

gain of function, therefore dominant (or neomorph)

Question 9

what type of mutation is PINK1

Answer 9

loss of function

Question 10

what type of mutation is synuclein

Answer 10

ante/neomorph

Question 11

what does parkin act as

Answer 11

a ubiquitin ligase

Question 12

5 research approaches

Answer 12

• reduce LRKK2 kinase activity
• find small molecules that activate parkin/pink1 pathway
• inhibit synuclein expression
• enhance synuclein aggregate removal
• stem cells to replace dopaminergic neurones

Question 13

treatment of PD

Answer 13

• L-dopa given by dopa decarboxylase inhibitor

- deep brain stimulation, electrodes planted into sub-thalamic nucleus