A conjugate composed of nerve growth factor coupled to a non-toxic derivative of Clostridium botulinum neurotoxin type A can inhibit neurotransmitter release in vitro.
Nerve growth factor (NGF) receptor binding, internalisation and transportation of NGF has been identified as a potential route of delivery for other molecules. A derivative of Clostridium botulinum neurotoxin type A (LHN) that retains catalytic activity but has significantly reduced cell-binding capability has been prepared and chemically coupled to NGF. Intact clostridial neurotoxins potently inhibit neurotransmitter release at the neuromuscular junction by proteolysis of specific components of the vesicle docking/fusion complex. Here we report that the NGF-LHN/A conjugate, when applied to PC12 cells, significantly inhibited neurotransmitter release and cleaved the type A toxin substrate. This work represents the successful use of NGF as a targeting moiety for the delivery of a neurotoxin fragment.
Chaddock
J A
JA
Centre for Applied Microbiology and Research, Porton Down, Salisbury, Wiltshire, UK.
Purkiss
J R
JR
Duggan
M J
MJ
Quinn
C P
CP
Shone
C C
CC
Foster
K A
KA
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D020932:Nerve Growth Factor; D019274:Botulinum Toxins, Type A; D009638:Norepinephrine