Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
29 Cards in this Set
- Front
- Back
|
What are the early symptoms of HD? (8 of them)
|
- Cognitive dysfunction
- Coordination problems - Depression - Impulsiveness - Irritability - Jerky eye movements - Psychotic symptoms - Sudden movements of fingers, limbs and trunk |
|
|
What are the late symptoms of HD? (3 of them)
|
- Choreiform movements (brief, sudden random twitchlike movements)
- Progressive cognitive decline, including memory loss and dementia - Mood swings, depression and apathy |
|
|
Is HD a late onset, inherited neurodegenerative disorder?
|
Yes
|
|
|
What is the mean age of onset for HD?
|
40
|
|
|
What is the cause of HD?
|
Defect in the gene that encodes the Huntingtin protein (autosomal dominant disorder, meaning one defective copy is enough to develop the disorder)
|
|
|
How many people are affected in the US?
|
30,000
|
|
|
Is the prevalence higher in whites or Asians/Africans?
|
whites
|
|
|
True or false: The Huntingtin protein function is not actually known but appears to be developmentally important because mice deficient in htt do not survive.
|
True
|
|
|
Does increased or decreased wild type htt protect neurons from death in response to toxic stimuli?
|
Increased
|
|
|
Is wild type htt a pro or anti apoptotic protein?
|
Anti-apoptotic
|
|
|
What is the effect of increased wild type htt on BDNF?
|
It increased the transcription of BDNF which helps neurons to survive and modulates synaptic plasticity
|
|
|
What is the effect of increased wild type htt on vesicular transport?
|
Enhances vesicular transport
|
|
|
What is the effect of decreased wild type htt in knockout mice?
|
The mice die in embryonic ages
|
|
|
Wild type htt expression below what percentage results in abnormal brain development?
|
Less than 50%
|
|
|
What happens when the htt gene is knocked out in post-mitotic neurons?
|
It causes apoptosis
|
|
|
What is HD?
|
An autosomal dominant disorder caused by a mutation in the htt gene
|
|
|
In HD, an expansion of CAGs in the coding region of the htt gene results in what?
|
More than 39 and up to 86 GLUs in affected individuals
|
|
|
How many CAGs do healthy subjects have and how many lead to very late onset of the disease?
|
36; 36-39
|
|
|
Increased CAG is though to be a gain or loss of function mutation?
|
Gain of function, the increased CAG repeats confer a new, toxic function to htt
|
|
|
Once repeats expand beyond 40 copies, they tend to increase from generation to generation causing what?
|
Earlier onset in the offspring than the parents; increased expansion of this repeat is also associated with more severe symptoms
|
|
|
Which neurons are the first to die?
|
The medium spiny neurons in the caudate and putamen (striatum), which project to the globus pallidus and substantia nigra
|
|
|
Is there neuronal loss in the following:
Cortex Thalamus Midbrain DA neurons Striatal cholinergic neurons |
Yes
Yes No No |
|
|
Is there evidence that there is striatal atrophy before diagnosis in HD?
|
Yes, striatal atrophy is detected more than 15 years prior to estimated diagnosis
|
|
|
MAKE SURE TO KNOW THE AFFECTED PATHWAYS
|
.
|
|
|
What is the process that makes mutant htt toxic?
|
- Proteolysis of mutant htt by caspases leads to generation of fragments
- Fragments aggregate in the nucleus and neuronal processes - MOST studies suggest that aggregates prevent the function of proteins and therefore cause neurotoxicity - However, SOME studies suggest that aggregates can sequestrate the soluble mutant htt and thereby play a neuroprotective role - But soluble htt in the cytoplasm can also cause abnormal interactions with other proteins |
|
|
LOOK AT SLIDES 18-22
|
.
|
|
|
Is there a cure for HD?
|
No
|
|
|
Which medications are used to dampen chorea?
|
DA antagonists like haloperidol
|
|
|
Which medications are used for the treatment of hyperkinesia in HD?
|
Tetrabenazine promotes metabolic degradation of DA
|
