Abstract:Clostridial neurotoxins reversibly
block neuronal communication
for weeks and months. While these proteolytic neurotoxins hold great
promise for clinical applications and the investigation of brain function,
their paralytic activity at neuromuscular junctions is a stumbling
block. To redirect the clostridial activity to neuronal populations
other than motor neurons, we used a new self-assembling method to
combine the botulinum type A protease with the tetanus binding domain,
which natively targets central neur… Show more
“…Recombinant atoxic mutants, made by Escherichia coli, can be engineered quickly and efficiently as useful vehicles for delivery to central neurons (Li et al, 2001). Using protein stapling technology, a chimera of botulinum neurotoxin A and the tetanus binding domain was created to specifically target CNS function and spare the neuromuscular junction (Ferrari et al, 2013). By limiting muscle paralysis, this may be useful for the future treatment of epilepsy or chronic pain.…”
Section: B Cleavage Of Snares By Clostridial Toxinsmentioning
“…Recombinant atoxic mutants, made by Escherichia coli, can be engineered quickly and efficiently as useful vehicles for delivery to central neurons (Li et al, 2001). Using protein stapling technology, a chimera of botulinum neurotoxin A and the tetanus binding domain was created to specifically target CNS function and spare the neuromuscular junction (Ferrari et al, 2013). By limiting muscle paralysis, this may be useful for the future treatment of epilepsy or chronic pain.…”
Section: B Cleavage Of Snares By Clostridial Toxinsmentioning
“…After intrathecal injection of this stapled toxin (100 ng), it inhibited mechanical hypersensitivity in a rat model of CFA-induced inflammatory pain. Interestingly, such a high concentration did not produce any paralysis (flaccid or spastic) [65]. This inventive methodology offers a versatile platform for attaching different ligands to the VAMP component, which display abilities to target various cell types or subpopulation [66].…”
Section: Retargeting Of Bont Variants To Selected Secretory Cells Formentioning
confidence: 99%
“…It binds to cultured hippocampal neurons, enters, and cleaves SNAP-25 with a potency only threefold less than BoNT/A. Substitution of H C /A with H C /TeTx created another variant [65]. After intrathecal injection of this stapled toxin (100 ng), it inhibited mechanical hypersensitivity in a rat model of CFA-induced inflammatory pain.…”
Section: Retargeting Of Bont Variants To Selected Secretory Cells Formentioning
“…Retargeting of CNTs to different neuronal populations other than MNs was achieved by a new self-assembling method, which enables the stapling of the BoNT/A protease with H C T [183]. Both recombinant proteins were produced separately and assembled using protein stapling technology, which exploits the high-affinity interaction of paired SNARE motifs [183].…”
Section: Protein and Gene Transfer Via Tentmentioning
confidence: 99%
“…Both recombinant proteins were produced separately and assembled using protein stapling technology, which exploits the high-affinity interaction of paired SNARE motifs [183]. Mechanical hypersensitivity was observed as a result of introducing the stapled chimera into a rat model of inflammatory pain, and neuronal activity was blocked in a specific area of the visual cortex [183].…”
Section: Protein and Gene Transfer Via Tentmentioning
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