Huntington's and motor neuron disease

Question 1

Huntington’s disease symptoms

Answer 1

Involuntary movements
Muscular and vocal tics
Slow or abnormal eye movement
Difficulty with speech or swallowing
Death within 15-20 years of symptoms

Question 2

HD pathology

Answer 2

Severe loss of neurons in caudate-putamen (basal ganglia)
Enlargement of lateral ventricles
Gliosis

Question 3

HD transmitter alterations

Answer 3

Glutamate excitotoxicity
Deficits in cholinergic and GABAergic neurons in caudate-putamen
Increased dopamine in early stages and decreased in late stages

Question 4

Huntington gene

Answer 4

IT-15 in chromosome 4
Encodes huntingtin 
Unknown function (may be TF)
Expansion of CAG repeats in exon 1 
Expansion length determines penetrance, severity and age of onset

Question 5

Huntingtin

Answer 5

PolyQ (polyglutamine) tract begins at AA 18
Htt with expanded polyQ fragments forms aggregates similar to amyloid fibrils
Form oligomers, intermediates and fibrils
Form fibrils when more than 30 repeats

Question 6

HD treatment

Answer 6

Depletion or stabilisation of dopamine and serotonin
Antioxidants
Stem cell therapy
IT-15 gene silencing

Question 7

Motor neuron disease

Answer 7

Also called Amyotrophic lateral sclerosis
Muscle atrophy, weakness and twitch (amyotrophic)
Glial scar in lateral columns of spinal cord (lateral sclerosis)
Death due to respiratory failure

Question 8

Familial MND

Answer 8

Accounts for 10%. Sporadic cases are 90%
20% of familial MND due to mutations in Cu/Zn superoxide dismutase (SOD1)
Also mutations in DNA/RNA binding proteins (FUS)
GGGGCC repeat expansion in C9orf72 (40% of familial cases)

Question 9

MND risk factors

Answer 9

Metals, pesticides and viruses (environmental)
Professional athletes, farmers (occupational)
Head trauma, smoking, obesity (lifestyle)

Question 10

MND treatment

Answer 10

Riluzole (glutamate antagonist)

Edaravone (antioxidant) delays motor deterioration