5: Motor Neuron Disease `

Question 1

What does motor neuron disease mean?

Answer 1

A group of neurodegenerative diseases

Question 2

What diseases are included in the MND umbrella?

Answer 2

ALS
PLS
PMA
Lou Gehrigs
PBP

Question 3

What occurs in the progression of ALS?

Answer 3

1. Motor neuron degeneration
2. Reduced signals to muscles
3. NMJ is disrupted
4. Muscle wasting and weakness
5. Progressive paralysis

Question 4

How long does progression take for ALS to become fatal?

Answer 4

Within 2-5 years of symptomatic onset

Question 5

What are the two types of onset for ALS?

Answer 5

Spinal/limb
Bulbar

Question 6

What are the symptoms of limb/spinal onset als?

Answer 6

Muscle stiffness and cramps
Muscle twitching
Weakness in arms legs hands and feet
Poor grip strength

Question 7

What are the symptoms of bulbar onset ALS?

Answer 7

Degeneration of corticobulbar tract
Wasting/weakness/fasciculations
Difficulty swallowing
Pooling of saliva
Spasm of vocal cords
Slow or slurred speech
Worse prognosis due to respiratory infections

Question 9

What are the cognitive symptoms of ALS?

Answer 9

Episodic memory impairments
15% develop frontotemporal dementia
Atrophy of frontal and temporal lobes
Personality changes/language disorder

Question 10

What percent of ALS is hereditary?

Answer 10

5-10 %

Question 11

What are the two types of ALS?

Answer 11

FALs and SALs

Question 12

What is FTD?

Answer 12

Frontotemporal dementia

Question 13

Diseases in what genes can cause ALS?

Answer 13

SOD1
C9orf72
TARDBP

Question 14

What was the first ALS causing mutation to be discovered?

Answer 14

SOD1

Question 15

What percent is caused by SOD1?

Answer 15

10-20%

Question 16

What is sod1?

Answer 16

Copper zinc superoxide dismutase 1

Question 17

What is copper zinc superoxide dismutase 1?

Answer 17

An antioxidant enzyme that breaks down superoxide radicals

Question 17

Where is copper zinc superoxide dismutase 1 found?

Answer 17

Cytosol
Mitochondria
Nucleus
ER

Question 18

What is the most common SOD1 mutation?

Answer 18

Missense

Question 19

What is tofersen?

Answer 19

Antisense treatments

Question 20

What mutation is the most common cause of ALS?

Answer 20

C9orf72 mutation

Question 21

What other disease can c9orf72 cause?

Answer 21

Frontotemporal dementia

Question 22

What type of c9orf72 mutation causes ALS?

Answer 22

GGGGCC repeat expansion in either intron 1 or promotor region (non coding region)
If in promotor this can reduce the amount of expression of c9orf72
Expansion gets transcribed

Question 23

What are the most common protein inclusions in ALS?

Answer 23

SOD1 and TDP-43

Question 24

In ALS, how does protein aggregation in neurodegeneration occur?

Answer 24

Insoluble intraneuronal protein aggregates Proteins are ubiquitinated and phosphorylated However not broken donw