Flashcards in 18: ALS Deck (11):
3 known risk factors for ALS
age, gender (1.5 male to 1 female). family history.
5 possible risk factors for ALS
athleticism. exposure to heavy metals, herbicides, chemicals. smoking. trauma. gulf war service.
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
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 causes of MN death in ALS
protein aggregation. cytoskeletal derangement. inflammation. glutamatergic excitotoxicity. oxidative stress.
what things normally prevent aggregation
chaperones like HSP79. proteasomes.
protein aggregation; 3 effects
loss of function of aggregated proteins. chaperone activity reduced. protesosome activity reduced. "choking"
cytoskeleton derangement: 2 things?
mSOD1 aggregates saturate/chock chaperones = inhibit transport. neurofilament disorganization, associated with hyperphosphorylation.
excitotoxicity: normal receptors?
AMPA: usually have GluR2 subunit which has low Ca permeability (Q converted to R during post trans. mod)
excitotoxicity: AMPA receptors in ALS?
abnormal unedited GluR2 Q isoform is highly permeable to Ca