Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis

Nemanić, Dalia; Mustapić, Matej; Matak, Ivica; Bach-Rojecky, Lidija

doi:10.1016/j.ejphar.2023.176279

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…Although this must be experimentally confirmed, we can postulate that the lower ability of BoNT/E to undergo such a phenomenon could be due to a potential targeting of other types of cargo less involved in neuronal transport. Many works support the importance of neuronal transport in the antinociceptive activity of BoNT/A [20,45,46]. As such behavior is limited in BoNT/E, it might restraint its therapeutic use for such conditions, maybe explaining the paucity of published data on the subject.…”

Section: Spread and Neuronal Transportmentioning

confidence: 99%

Intramuscular Botulinum Neurotoxin Serotypes E and A Elicit Distinct Effects on SNAP25 Protein Fragments, Muscular Histology, Spread and Neuronal Transport: An Integrated Histology-Based Study in the Rat

Martin,

Carre,

Bilbault

et al. 2024

Toxins

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Botulinum neurotoxins E (BoNT/E) and A (BoNT/A) act by cleaving Synaptosome-Associated Protein 25 (SNAP25) at two different C-terminal sites, but they display very distinct durations of action, BoNT/E being short acting and BoNT/A long acting. We investigated the duration of action, spread and neuronal transport of BoNT/E (6.5 ng/kg) and BoNT/A (125 pg/kg) after single intramuscular administrations of high equivalent efficacious doses, in rats, over a 30- or 75-day periods, respectively. To achieve this, we used (i) digit abduction score assay, (ii) immunohistochemistry for SNAP25 (N-ter part; SNAP25N-ter and C-ter part; SNAP25C-ter) and its cleavage sites (cleaved SNAP25; c-SNAP25E and c-SNAP25A) and (iii) muscular changes in histopathology evaluation. Combined in vivo observation and immunohistochemistry analysis revealed that, compared to BoNT/A, BoNT/E induces minimal muscular changes, possesses a lower duration of action, a reduced ability to spread and a decreased capacity to be transported to the lumbar spinal cord. Interestingly, SNAP25C-ter completely disappeared for both toxins during the peak of efficacy, suggesting that the persistence of toxin effects is driven by the persistence of proteases in tissues. These data unveil some new molecular mechanisms of action of the short-acting BoNT/E and long-acting BoNT/A, and reinforce their overall safety profiles.

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Section: Spread and Neuronal Transportmentioning

confidence: 99%