28 - Neurotoxins II Flashcards
paraquot
herbicinde, similar structure to MPTP: works on ETC to kill plants + produces PD like symptoms in people
animal toxins: specificity? can be used for? also useful in?
highly selective for specific protein targets in NS. specifically interfere with certain processes. isolation of membrane proteins + channels
tetrodotoxin
fugu poison from japanese puffer fish, blocks Na+ channel, paralysis
saxitoxin
dynoflagelates in red tide: blocks Na+ channel, paralysis
conotoxin gvia: from? effect? therapy?
from cone snail, blocks N type ca channels and stops neurotransmission. treats chronic opioid resistant pain
agatoxin IVA
funnel web spider, blocks P type Ca channels = stops neurotransmission
charybdotoxin
from scorpions: blocks Ca-activated K channels = mast cell depolarization + degranulation, activation of sensory nerve endings = pain
a bungarotoxin
from banded krait snake, blocks nAChR
nAChR structure?
5 subunits, each with 4 TMDs.
what nAChR and what toxin?
a bungarotoxin for adult muscle. conotoxin and k-bungarotoxin for ganglionic. a conotoxin for CNS/sensory.
tetanus toxin: from? enters at? transported to?
from clostridium tetani bacteria. enters at NMJ, transported to CNS (Retrograde transport)
tetanus toxin: effect (2)
stops spinal neurons from releasing GABA/glycine (inhibitory NTs). degrades presynpatic protein synaptobrevin.
tetanus toxin: symptoms/signs?
generalized contractions of agonist + antagonist musculature = tetanic spasm. lock jaw = rigid paralysis.
botulinum toxin: from? causes? structure?
group of toxins from clostridium botulinum bacteria. causes paralysis associated with botulism/food poisoning. 2 chain polypeptide: heavy chain + light chain
botulinum toxin: LD50? blocks?
0.005 to 0.05 ug per kg. blocks NT release
botulinum toxin mechanism of heavy + light chains
light chain = protease that attacks fusion proteins in presynp terminals = prevent NT release. heavy chain targets toxin to nerve endings.
botulinum toxin: overall effect
prevents ACh release at NMJ = flaccid/sagging paralysis of muscles
SNARE hypothesis: proteins expressed where? which proteins?
expressed on vesicles + plasma membrane, permit fusion of lipid bilayers. t SNARES = syntaxin + SNAP 25. v-SNARE = synaptobrevin
SNARE hypothesis: what is favorable?
thermodynamically very favourable for syntaxin, SNAP 25 and synaptobrevin to form a 1:1:1 complex
evidence for snare hypothesis?
baterial toxins like botox stop transmitter release by preventing vesicle fusion, contain variety of proteases that target SNAP 25, synaptobrevin + syntaxin
4 uses of botox
incontidence, intractible pain (diabetic neuropathy), hyperhidrosis, cosmetics.
