Lecture 22

Question 1

The most common form of MND is

Answer 1

amyotrophic lateral sclerosis

Question 2

___ forms of MN are affected in MND

Answer 2

both

Question 3

True or False

All MN disease are progressive and ultimately fatal

Answer 3

True

Question 4

Symptoms of NMD are:

Answer 4

Muscle twitching
Muscle weakness
Difficulty Speaking
Difficulty swallowing
Tripping, stumbling, dropping things
Progressive paralysis
Decreased respiratory function

Question 5

peak age of onset is…

Answer 5

45-60 years

Question 6

Muscle atrophy can occur later on - causing a loss of muscle ____

Answer 6

Muscle mass

Question 7

True or False

There is no diagnostic test for MND

Answer 7

true

Diagnosis is purely clinical - a process of exclusion

Question 8

The timeframe for symptom progression is ________

Answer 8

variable

Question 9

There is usually a lack of ____ in terms of muscle atrophy

Answer 9

There is usually a lack of symmetry in terms of muscle atrophy

Question 10

With the drug, Rilutek - there is no correlation between ___ and _____ ______

Answer 10

With the drug, Rilutek - there is no correlation between dose and clinical outcome

Question 11

The majority of cases of MND are _____, meaning no ____ _____,

Answer 11

The majority of cases of MND are sporatic, meaning no family history, very sudden

Question 12

Mutations in Cu/Zn ______ ________ gene associated with familial amyotrophic lateral sclerosis

Answer 12

Mutations in Cu/Zn superoxide dismutase (SOD1) gene associated with familial amyotrophic lateral sclerosis

Question 13

Cu/Zn superoxide dismutase is expressed in all cells - true?

Answer 13

yes

Question 14

the primary role of Cu/Zn superoxide dismutase is to ..

Answer 14

detoxify toxic superoxide radicals

Major anti-oxidant enzyme in the body

Question 15

Cu/Zn superoxide dismutase has about __ AAs and binds one __ ion and one ___ion

Answer 15

Cu/Zn superoxide dismutase has about 150 AAs and binds one copper ion and one zinc ion

Question 16

it is believed that _______ mutations in SOD1 cause MND

Answer 16

substitution

Question 17

True or False

You get MND due to a loss of fnction of SOD1

Answer 17

False

it is a toxic gain of function

Question 18

What are some possible cause of how mutant SOD1 causes MND?

Answer 18

Abberant pro-oxidant gain of function

Protein midfolding

Protein aggregation

Mitochondrial dysfunction

Question 19

Approximately ___% of MND cases are sporadic

Answer 19

Approximately 90% of MND cases are sporadic

Question 20

10% of the familial cases of MND most are autosomal ______

Answer 20

dominant

Question 21

SOD1 mutation mouse models can be used to study MND - this has shown the the more mutant SOD1…

Answer 21

the more severe motor neuron pathology = more severe phenotype

but maybe not!! It depedns what state SOD1 is in

Question 22

Prospective drug has been shown to ______ the levels of mutant SOD1

Answer 22

Prospective drug has been shown to increase the levels of mutant SOD1

but the mice get better…?!

Question 23

The SOD1 protein exists in 3 different states:

Answer 23

Apo - No metals (barely exists - degraded rapidly)

Metal-deficient = one but no the other

Holo = both metals (normal functional form)

Question 24

It is possible that ‘drug’ causes an _______ in the normal state of SOD1 by adding __ to the spinal cord

Answer 24

It is possible that ‘drug’ causes an increase in the normal state of SOD1 by adding Cu to the spinal cord