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

Abstract 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-bi...

Full description

Saved in:
Bibliographic Details
Published in:Growth factors (Chur, Switzerland) Switzerland), 2000, Vol.18 (2), p.147-155
Main Authors: Chaddock, John A., Purkiss, John R., Duggan, Michael J., Quinn, Conrad P., Shone, Clifford C., Foster, Keith A.
Format: Article
Language:English
Subjects:
Animals
Botulinum toxin type A
Botulinum Toxins, Type A - pharmacology
Dose-Response Relationship, Drug
Drug Delivery Systems - methods
nerve growth factor
Nerve Growth Factor - pharmacology
Neurons - drug effects
Norepinephrine - secretion
PC12 Cells
Rats
synaptosomal-associated protein 25
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract 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.
ISSN:0897-7194
1029-2292
DOI:10.3109/08977190009003240