huntington's

Question 1

symptoms

Answer 1

involuntary movement (chorea)
speech problems
personality and brain changes

Question 2

pathological features

Answer 2

• neuronal cell loss in caudate nucleus and putamen in striatum
• also cell loss in basal ganglia; hypothalamus; brain stem
• affecting medium spiny neurons of the striatum
• mutation in huntingtin protein

Question 3

HD risk, repeats

Answer 3

• 40+; high penetrance > HD with age
• 36-39; high risk of HD
• 37-35; low risk of HD
• <27; no risk
  more repeats develop earlier in life CAP-score

Question 4

stages

Answer 4

• presymptomatic; prior to detectable symptoms
• predromal; subtle changes in patient without formal disease diagnosis
• formal clinical diagnosis
• fatal outcome

Question 5

formation of HTT fragments

Answer 5

• cleavage by proteases in the HTT flexible regions; mutant proteins gets a slightly different structure that is more prone to cleavage to toxic fragments
• error during splicing of different exons, leading to aggregation and toxicity

Question 6

gain of toxic function

Answer 6

loss of HTT native function, disruption of cell process.
protein changes in structure and thereby gains a new function, that is toxic to the cell
in many protein aggregation diseases

Question 7

prion-like propagation

Answer 7

amyloid-like misfolded proteins, filament structure. can catalyze the formation of more filaments.
At what speed the brain generates more filaments, tell use how much filaments where already present

Question 8

tetrabenazine

Answer 8

inhibitor of synaptic vesicular amine transporter

Question 9

therapy of symptoms

Answer 9

depakote; mood, chorea
neuroleptics and creatine; against weight loss
amantadine; chorea, fatigue

Question 10

treatment strategies

Answer 10

• Huntingtin lowering
• Inhibiting pathogenic protein aggregation
• modifying huntingtin life cycle
• downstream strategies