Neurodegeneration Five - Huntingtons Flashcards
(27 cards)
What is the htt protein used for?
- Transport
- antiapoptotic functions
What happens to mutant htt?
accumulations of the protein are called inclusions and these are heavily ubiquitinated(small protein attatched to it) - identifiable
In huntingtons do dying cells have inclusions?
Most dying cells and neurons do not have inclusions
Whats a macroscopic observation of huntingtons?
Marked cerebral atrophy
Whats some microscopic observations of huntingtons?
- Neurons that use gaba are preferentially affected
- Medium spiny neurons
Can huntingtons be inherited?
It is autosomal dominant (yes) therefore it depends on the number of CAG repeats as to dominance 40+ is full penetrance
On a genetic level what causes huntingtons?
expanded CAG region (codes for glutamate)
where is the htt gene located?
IT15 in the short arm of chromosome 4
whats the corrolation between CAG repeats and disease?
up to 35 = normal (20 is normal)
35-40 = gene carrier
40+ = full penetrance and HD
Whats the incidence of HD?
5 in 100,000 in NZ
When does HD onset?
Depends on the extent of CAG repeats as to its insensity and onset, but typically 35-45years
What are the symptoms of HD?
- Hyperkinesia/rigidity
- CHOREA (Involuntary movements) - extrapyramidal movements
- Behavioural and cognition changes (first symptom)
- Athetosis (bodies midline is displaced)
Is htt asymetric?
It is a disease of the basal ganglia in boths hemispheres
What do basal ganglia control?
Mood and movement
Does chorea occur in sleep?
No
What does the loss of medium spiny nuerons lead to?
GPi neurons are tonically active
Is there a sequence of cell loss in the basal ganglia?
Yes
What is the cell loss sequence?
medium spiny gaba neurons are preferentially lost starting with:
1) Striatum - GPe loss
= Loss of gaba, decreased inhibition of thalamus, hyperkinesia
2) Striatal - nigral neurons are loss
3) Straital - GPi neurons lost
= loss gaba (GPI), increased inhibition of thalamus = rigidity
What does number of CAG repeats correlate with?
- Age of onset, intensity and pathology
Whats the treatment for htt?
No drugs work
- can relieve some symptoms i.e antidepressants
- gene therapy
- neural tranplants
Is either gender preferentially affected?
No
What is htt associated with?
Genetic anticipation
What is genetic anticipation?
Some repeats are inherited
- Mum = ~4
- Dad = up to 7
- Paternal age = longer repeats, due to the quality of sperm and eggs
What neurons are lost first in htt?
Gaba MSN projecting from the striatum to the GPe thus the indirect pathway (via SNT) becomes tonically active (no inhibiton)
