Neuro Pharm profs

Question 1

Half of neurons die in development via apoptosis. A lack of trophic support can cause this. What does this pathway to apoptosis look like?

Answer 1

• lack of trophic support
• activates jun kinase
• induces DP5 activating BAX
• Bax of BCL2 fam mediates release of Cyt C from mito
• Cyt C activates caspase 9
• caspase 9 activates caspase 3
• caspase cascade induces apoptosis

Question 2

Neurotrophic Factors promote neuronal survival. Neurotrophins are required for sympathetic and sensory neurons. What family of receptors do they bind? What are their specific matches?

Answer 2

• TRK fam of receptors
• TRK - NGF
• TRKB - BDNF, NT-4/5, NT-3
• TRKC - NT-3

Question 3

What do protein tyrosine kinase receptor binding proteins bind?

Answer 3

SH2 and PTB domains

Question 4

What converts inactive RAS to active RAS?

Answer 4

SOS in close proximity with GEF

Question 5

What happens once SOS and GEF have converted RAS to active form?

Answer 5

activated RAS binds serine-threonine PK (Raf1)

Raf1 activates MEK activates MAPK

MAPK gets transported to nucleus and regulates transcription factors

Question 6

What turns off RAS? What is the pathology if this does not happen?

Answer 6

a GTPase Activating Protein (GAP) turns off RAS normally

If RAS cannot turn off, we might have a LOF mutation causing Neurofibromatosis type I - activation of growth pathways that cause tumors

Question 7

Axons are guided in their growth by a growth cone, a sensory-motor structure that responds to guidance cues. What are some cues it may receive?

Answer 7

netrin can cause growth cone attraction

receptors are DCC (growth cone grows toward/attracted) and UNC5 (repulsion)

Question 8

The activation of D1 receptors in responsed to a growth cone receptor will cause what?

Answer 8

attraction - D1 receptors will increase cAMP and PKA, increase DCC insertion into membrane

Question 9

The activation of D2 receptors in regard to growth cone will cause what?

Answer 9

repulsion - D2 activated will decrease cAMP and PKA, increasing UNC5

Question 10

What is the difference between nAChRs and mAChRs?

Answer 10

nAChRs are ligand gated ion channels

mAChRs are GPCRs

Question 11

What triggers the clustering of AChRs to form part of a NMJ? What does this do exactly and what else is required?

Answer 11

agrin

increase activity of MuSK

rapsyn (cytoskeleton protein) also required for clustering

Question 12

What upregulates AChR synthesis?

Answer 12

neuregulin and ErbB - activates Erb B TK inducing AChR synthesis

Question 13

What inhibits synthesis of AChRs from distant nuclei so you don’t have NMJs forming just anywhere?

Answer 13

electrical activity

Question 14

What purine analog will inhibit the synthesis of nucleic acids and tx MG chronically, but has a delayed onset of 6-12 months?

Answer 14

Azathioprine

Question 15

What do I not want to give to anyone with GI botulism? Why?

Answer 15

Aminoglycosides, can cause NMJ blockade; cell lysis will increase toxin in the body

Question 16

What do I tx infant botulism with?

Answer 16

Human-derived Botulism immune globulin (BIG-IV)

Question 17

What drugs inhibit K channel efflux, increasing AP duration, ultimately allows Ca channels to be open longer? What is this used for?

Answer 17

Amifampridine; 3,4 DAP

Lambert Eaton Syndrome

Question 18

What should be included in my first line tx of MG? What is the MOA?

Answer 18

pyridostigmine or neostigmine

AChE inhibitor, increasing the ACh concentration at the NMJ

Question 19

What drugs could be given for chronic immunopathies that would limit the production of IL-2 and inhibit Th cells and lower T lymphocyte response?

Answer 19

cyclosporine and tacrolimus

Question 20

What do I tx malignant hyperthermia with? What is the MOA?

Answer 20

dantrolene IV

inhibits Ca leak to stop uncontrolled contractions (inhibits Ryanodine Receptor Calcium Release channel)

Question 21

What two genes might predispose someone to malignant hyperthermia?

Answer 21

MHS1 and MHS5