Lecture 8: Huntington's Disease

Question 1

HD

Answer 1

• Hyperkinetic disorder
• Autosomal dominant
• Usually ‘late onset’: 30-40s
• Indirect pw mostly affected

Question 2

HD:genetics

Answer 2

• Huntington gene (C4) codes for huntington protein
• Gene includes a trinucleotide repeat (CAG)
• Repeated part of the gene is known as the polyQ region
• > 36 repeats = mutant HTT
• The longer the polyQ tract, the earlier onset

Question 3

HD: Macroscopic

Answer 3

• WS loss of MSNs in striatum,
• cortical and striatal atrophy
• ventricular enlargement

Question 4

HD: microscopic

Answer 4

• Inclusion bodies

Question 5

Pathways

Answer 5

• Direct: promotes execution of planned motor function (cortex is excited)
• Indirect: inhibits execution of motor function

Question 6

PD vs HD movement

Answer 6

PD: hypokinetic
HD: hyperkinetic

Question 7

PD vs HD Basal ganglia

Answer 7

PD: loss of dopamine neurons in BG
HD: loss of MSNs in striatum

Question 8

PD vs HD pathways

Answer 8

PD: reduced activity of direct pw and increased activity of indirect pw
HD: increased dopamine, decrease GABA and ACh -> affect neurons of indirect pw (-> reduced inhibition of movement)

Question 9

HD: treatments

Answer 9

• Only to reduce symptoms
• Antidepressants for depression
• Benzodiazpeines for muscle relaxation
  Tetrabenazine for cholera

Question 10

Future therapies

Answer 10

• Gene silencing

- CRISPR/Cas9: gene editing technology