18: ALS Flashcards Preview

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Flashcards in 18: ALS Deck (11):
1

3 known risk factors for ALS

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

2

5 possible risk factors for ALS

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

3

toxicity and levels of SOD1?

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

4

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

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

5

5 causes of MN death in ALS

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

6

what things normally prevent aggregation

chaperones like HSP79. proteasomes.

7

protein aggregation; 3 effects

loss of function of aggregated proteins. chaperone activity reduced. protesosome activity reduced. "choking"

8

cytoskeleton derangement: 2 things?

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

9

excitotoxicity: normal receptors?

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

10

excitotoxicity: AMPA receptors in ALS?

abnormal unedited GluR2 Q isoform is highly permeable to Ca

11

glutamatergic excitoxicity: lose what?

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