ALS

Question 1

ALS

Answer 1

Amyotrophic
Lateral Sclerosis

Question 2

ALS definition

Answer 2

Neurodegenerative disease effecting
the upper and lower motor neurons

Question 3

types

Answer 3

sporadic- more common
familial- more known

Question 4

potential causes

Answer 4

genetics
environmental
age
sex(male)

Question 5

Genetics

Answer 5

-Mutations in genes such as SOD1 and C9orf72

**Just because one has these mutations ≠ onset of
disease

Question 6

Environment

Answer 6

Exposure: heavy metals, neurotoxins, electromagnetic fields, and pesticides

Question 7

Liquid-Liquid Phase Separation

Answer 7

protein aggregation dynamic within the cell

Question 8

ALS liquid-liquid

Answer 8

dynamic is thrown off and is abnormal,
pushing more towards a heightened amount of protein
aggregation within the cell.

Question 9

Nuclear Pore complex normal function

Answer 9

acts as the gate keeper into the
nucleus. It allows proteins and RNA to enter/exit the cell when needed

Question 10

ALS nuclear pore complex

Answer 10

abnormal and leads to
incorrect distribution of proteins and RNA within
the cell, leading to damage.

Question 11

TDP43 full name

Answer 11

TAR DNA Binding Protein 43

Question 12

TDP43 location due to ALS

Answer 12

normally located inside of the nucleus
* Has been displaced into the cytoplasm and forms into
large protein aggregates that are toxic to the cell

Question 13

26s proteasome

Answer 13

the 26S proteasome is inhibited when it attempts to break this down leading to the buildup of toxic
“trash” inside of the cytoplasm

Question 14

SOD1 name

Answer 14

Superoxide dismutase 1

Question 15

SOD1 normal function

Answer 15

antioxidant enzyme

Question 16

SOD1 toxicity

Answer 16

1) protein aggregation
2) mitochondrial dysfunction
3) Oxidative stress
4) impaired proteostatis
5) excitotoxicity
6) Neuroinflammation

Question 17

C9orf72 Mutation

Answer 17

most common
It consists of a six-nucleotide repeat consisting of 4 guanine followed by 2 cytosine
* Generally, there are 2-30 of these repeats, but when mutated, there can be 4000+

Question 18

Mechanisms for disease

Answer 18

• RNA Toxicity
• Repeat-Associated Non-ATG Translation (RAN Translation)
• Loss of normal C9orf72 function

** All of these may happen at the same time, or they may not. It is still under research.