Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

NEUR0010 > Huntington's Disease > Flashcards

Huntington's Disease Flashcards

1
Q

What are the symptoms of adult-onset HD?

A 
Chorea - involuntary jerky movements
Loss of voluntary movement control
Gait and balance problems
Delayed saccades
Psychiatric symptoms (e.g. depression, psychosis)
Cognitive symptoms
Weight loss
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What type of inheritance pattern does HD have?

A

Autosomal dominant

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Which gene is mutated in HD?

A

HTT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

How many CAG repeats does the normal allele have?

A

1-26

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How many CAG repeats does the high normal allele have and what is the effect of this?

A

27-35
Neurological problems - but not HD -
Can expand in future generations - but no HD risk to individual

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How many CAG repeats does the reduced penetrance allele have and what is the effect of this?

A

36-39

Some do not develop HD - may be due to death before symptom presentation - limited by human lifespan

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How many CAG repeats does the abnormal allele have and what is the effect of this?

A

40+

Complete penetrance - causes HD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the relationship between CAG repeat length and age of HD onset?

A

Increased repeat length - decreased age of onset

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is anticipation?

A

More CAG repeats down generations

More severe and earlier disease onset down generations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How does anticipation occur?

A

DNA replication machinery slips back

Replicates same stretch of CAG repeats more than once

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How many CAG repeats are required for the mutant huntingtin with a different conformation to the WT?

A

36+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is likely to be the purpose of the hole in huntingtin?

A

Fit DNA within

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Name 4 physiological roles of huntingtin

A

Endocytosis
BDNF trafficking
Autophagy
Transcriptional regulation - via direct DNA interaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is the effect of huntingtin KO in mice?

A

Lethal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What are the species of huntingtin and which is the most toxic?

A

Soluble fibrils - most toxic

Insoluble aggregates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the effects of cytoplasmic huntingtin aggregates?

A 
Impair proteostasis (e.g. autophagy) - toxic proteins accumulates
Sequester chaperones - hinders protein folding
17
Q

How is the translocation huntingtin poly(Q) sequence altered in HTT mutants and what is the effect of this?

A

Poly(Q) sequence returns to nucleus

Forms insoluble nuclear aggregates - disrupt transcription

18
Q

In which cell type is cell death most prominent in HD?

A

GABAergic MSNs of striatum

19
Q

Which brain areas are affected by atrophy in HD?

A

All except cerebellum

20
Q

How do the symptoms of juvenile HD differ from those of adult-onset HD?

A

No chorea

Seizures

21
Q

What are the cognitive symptoms of HD?

A

Impulsivity
Irritability
Normal memory

22
Q

When do the cognitive symptoms of HD present?

A

≥10yrs before motor symptoms

23
Q

What is the effect of expressing only exon 1 of HTT in mice?

A

HD model - falls off rotarod, dies early

24
Q

How was it previously thought that huntingtin exon 1 fragment was formed?

A

Huntingtin cleaved - to toxic exon 1 protein

25
Q

How is it now thought that huntingtin exon 1 fragment is formed?

A

Aberrant splicing of HTT pre-mRNA

Excess CAG repeats in HTT predispose to early snipping - by affecting intron 1 splicing signals

26
Q

What is the effect of germline instability on HTT?

A

Intergenerational CAG repeat number changes

27
Q

What is the effect of somatic instability on HTT?

A

In some tissues repeat length increases during lifespan (e.g. striatum MSNs)
Can be different CAG repeat length in different tissues

28
Q

Which type of gene can modify HD onset and why?

A

DNA repair genes

DNA repair affects somatic instability

29
Q

Which factor do striatal MSNs require for survival?

A

BDNF

30
Q

Where is BDNF made and how is it transported to striatal MSNs?

A

Made in cortical cell bodies

Transported down corticostriatal axons

31
Q

How is BDNF affected in HD?

A

Decreased production

Less efficient trafficking - due to role of huntingtin in trafficking

32
Q

How do ASOs affect HTT?

A

Bind to HTT pre-mRNA
Destroy
Prevent HTT protein synthesis

33
Q

What was the effect of an HTT ASO in a human trial?

A

Decreased exon 1 mHTT protein in CSF
No serious side effects
Correlation between degree of mHTT protein decrease and clinical score change

34
Q

Name 2 future possible treatments for HD and what they target

A

RNAi - mHTT mRNA - prevent translation

Zinc finger proteins - HTT DNA - cut mutation out

35
Q

What is a possible problem with the current HTT ASO?

A

It blocks production of mutant and WT huntingtin

NEUR0010 (9 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions