18: ALS

Question 1

3 known risk factors for ALS

Answer 1

age, gender (1.5 male to 1 female). family history.

Question 2

5 possible risk factors for ALS

Answer 2

athleticism. exposure to heavy metals, herbicides, chemicals. smoking. trauma. gulf war service.

Question 3

toxicity and levels of SOD1?

Answer 3

toxicity not associated with levels of SOD1 enzyme activity (aka not because it’s not doing its normal job) but some gain of cytotoxic function

Question 4

what 2 groups of MNs not affected in ALS? why?

Answer 4

onuf’s nucleus and the oculomotor nucleus: have calcium buffering proteins calbindin and parvalbumin

Question 5

5 causes of MN death in ALS

Answer 5

protein aggregation. cytoskeletal derangement. inflammation. glutamatergic excitotoxicity. oxidative stress.

Question 6

what things normally prevent aggregation

Answer 6

chaperones like HSP79. proteasomes.

Question 7

protein aggregation; 3 effects

Answer 7

loss of function of aggregated proteins. chaperone activity reduced. protesosome activity reduced. “choking”

Question 8

cytoskeleton derangement: 2 things?

Answer 8

mSOD1 aggregates saturate/chock chaperones = inhibit transport. neurofilament disorganization, associated with hyperphosphorylation.

Question 9

excitotoxicity: normal receptors?

Answer 9

AMPA: usually have GluR2 subunit which has low Ca permeability (Q converted to R during post trans. mod)

Question 10

excitotoxicity: AMPA receptors in ALS?

Answer 10

abnormal unedited GluR2 Q isoform is highly permeable to Ca

Question 11

glutamatergic excitoxicity: lose what?

Answer 11

loss of Glu transporters aka EAATs which normally uptake/recycle glutamate