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Mastoparan-7 Rescues Botulinum toxin-A Poisoned Neurons in a Mouse Spinal Cord Cell Culture Model

Mastoparan-7 Rescues Botulinum toxin-A Poisoned Neurons in a Mouse Spinal Cord Cell Culture Model

Peng Zhang, Radharaman Ray, Bal Ram Singh, Prabhati Ray

Toxicon. 2013 Dec 15;76:37-43.

PMID: 24047963

Abstract:

Botulinum neurotoxin serotype A (BoNT/A) is the most potent poison of biological origin known to mankind. The toxicity of BoNT/A is due to the inhibition of neurotransmission at cholinergic synapses; this is responsible for the symptom of flaccid paralysis at peripheral neuromuscular junctions. At a molecular level, the BoNT/A effect is due to its inhibition of stimulated acetylcholine (ACh) release from presynaptic nerve terminals. Currently, there is no antidote available to rescue BoNT/A-poisoned synapses. Here, we report an example of rescuing botulinum-poisoned cultured mouse spinal cord neurons by treatment with Mastoparan-7 (Mas-7), which is known to be a phospholipase A2 activator compound. Mas-7, a naturally occurring bee venom peptide, was delivered to botulinum-poisoned neurons via a drug delivery vehicle (DDV) construct prepared using the recombinant non-toxic heavy chain (HC) fragment of BoNT/A itself. In this method, the BoNT/A HC component in the DDV served as a neuron specific drug targeting molecule. We found that Mas-7 delivered into BoNT/A intoxicated spinal cord cells restored over 40% their property of stimulated neurotransmitter release. Rescue from cell poisoning did not occur from inhibition of the endopeptidase activity of BoNT/A light chain (LC) against its well-known substrate, SNAP-25 that is mechanistically involved in the cholinergic neuroexocytosis process. Rather, Mas-7 induced a physiological host response apparently unrelated to SNAP-25, but linked to the phospholipase-mediated signal transduction pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP145854597	Mastoparan-7		145854-59-7	Price

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