Brainscape's Knowledge GenomeTM

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


See full index

Brain Function and Malfunction > SMA > Flashcards

SMA Flashcards

You may prefer our related Brainscape-certified flashcards:
The Brain flashcards
1
Q

when was SMA first described?

A

1891 by Werdnig and Hoffmann separately

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

onset of SMA and death

A

onset before 6 months and death by 2 years

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

what is SMA?

A

degeneration of lower, alpha motor neurones in ventral horn

progressive denervation and atrophy of skeletal muscle and paralysis

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

what muscles are particularly affected in SMA?

A

proximal

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

inheritance of SMA

A

autosomal recessive

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

what do 98% of patients have?

A

homozygous disruption of telomeric SMN1 gene

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

SMN1

A

survival motor neuron 1

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

what is SMN for?

A

essential for cell survival

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

what is SMN2?

A

centromeric SMN2 is identical but for a single nucleotide point mutation in exon 7 - truncated, unstable protein

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

incidence

A

1 in 6-10 000

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

what % of west are carriers?

A

2-3

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

type 1

A

severe, before 6 months, unable to sit, die by 2

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

type 2

A

7-18 months, never walk

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

type 3

A

after 18 months, live to adult

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

type 4

A

second or third decade, walk, die as adult

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

chromosome

A

5 (5 q 13)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

more copies of SMN2=

A

milder disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

for mouse models, SMN protein needs to be knocked down to what level?

A

20% normal

19
Q

mice SMA model

A

don’t have SMN2 - human SMN gene added

20
Q

incidental problem in rat studies

A

fail to gain weight - not fully explained as means bones not growing normally either

21
Q

SMN role in RNA processing

A

SMN associates with gemins of coiled bodies in assembly of SnRNPs - splicosome

22
Q

splicing in SMA

A

problems in splicing only appear at late stages of disease

23
Q

What is SMA otherwise known as

A

floppy baby syndrome

do not reach milestones

24
Q

histological staining findings in SMA

A

lose alot of synapses with every motor neuron

alot of denervated muscle - some hypertrophied muscles that remain

25
Q

Lower alpha motor neurons in SMA

A

fewer, not none

26
Q

Stain for SMN protein in SMA

A

low

27
Q

1st sign of SMA

A

lose nerve terminal at skeletal muscle

28
Q

more copies of SMN2 =

A

less severe disease

29
Q

SMN in axons

A

specifically regulated b-actin trafficking to nerve terminals
b-actin KO mice show no developmental or regenerative phenotype

30
Q

is motor system normal at birth?

A

appears to be - can’t differentiate control vs SMA mouse

formed all synapses normally then goes wrong

31
Q

what % motor neurones lost?

A

about 25-30% neurons lost

32
Q

why motor neurons?

A

largest neurons in the body
hyperexcitable
longest axons
inefficient splicing of SMN2

33
Q

Why are some motor neurons not affected?

A

not sure, some populations in same part of body survive and some don’t?

34
Q

Some examples of non-neuromuscular pathology

A

cardiac arrhytmias
peripheral necrosis
bone, pancreas, liver
clots - platelets high SMN

35
Q

hypoxia

A

exacerbates SMN deletion

36
Q

4 types of treatments and example

A

Gene therapy - zolgensma
HDAC inhibitors - risdiplam
Antisense oligonucleotide - spinraza

37
Q

Gene therapy

A

self complimentary AAV
normal copy SMN1
increase life span, not body weight
expensive - only need 1 as genetic

38
Q

HDAC inhibitors

A

regulators of transcription
increase SMN2 promoter activity
increase lifespan
non-targeted effect

39
Q

How do ASOs work?

A

bind to intronic splice silencers to promote inclusion of exon 7 in SMN2
increased length of protein

40
Q

spinraza FDA approval

A

types 1,2,3

intrathecally

41
Q

target of spinraza

A

ISS-N1

42
Q

zolgensma

A

FDA approved April 2019

43
Q

Non-SMN pathways in SMA

A

ubiquitin dependent pathways regulate NMJ pathologies in SMA
UBA1 and b-catenin
therapy with quercetin ameliorate neuromuscular symptoms
do not live longer

44
Q

Future of SMA

A

track those on spinraza
screening - therapies pre symptomatically
multiple therapies

Brain Function and Malfunction (7 decks)

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