AbobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA neurotoxin content and activity: potential implications for duration of efficacy in patients

Field, Malgorzata; Splevins, Andrew; Schans, Marcel van der; Langenberg, J.P.; Noort, Daan; Picaut, Philippe; Foster, Keith A.

doi:10.1016/j.toxicon.2018.11.082

Cited by 2 publications

(3 citation statements)

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“…To understand whether hTau secretion was dependent on the synaptic SNARE complex in neurons, as it was in isolated synaptosomes (Mazzo et al, 2022), we decided to first use BoNT/A to target SNAP25. We used a commercial formulation of BoNT/A, abobotulinumtoxinA (Dysport, Ipsen), which is used for the treatment of several pathologies characterised by neuronal hyperactivity (Field et al, 2018). Dysport differs from other commercial preparations (Botox, Allergan and Xeomin, Merz) in its manufacturing process and the excipients and doses used in humans (Foster, 2014;Pickett, 2014).…”

Section: Discussionmentioning

confidence: 99%

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

Panzi

Lazo²,

Surana

et al. 2023

Preprint

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Pathological tau aggregates propagate across functionally connected neuronal networks in human neurodegenerative pathologies, such as Alzheimer's disease. However, the mechanism underlying this process is poorly understood. Several studies have showed that tau release is dependent on neuronal activity and that pathological tau is found in the extracellular space in free form, as well as in the lumen of extracellular vesicles. We recently showed that metabotropic glutamate receptor activity and the SNAP25 integrity modulate the release of pathological tau from human and mouse synaptosomes. Here, we have leveraged botulinum neurotoxins (BoNTs), which impair neurotransmitter release by cleaving specific synaptic SNARE proteins, to dissect molecular mechanisms related to tau release at synapses. In particular, we have tested the effect of botulinum neurotoxin A (BoNT/A) on the synaptic release of tau in primary mouse neurons. Hippocampal neurons were grown in microfluidic chambers and transduced with lentiviruses expressing human tau (hTau). We found that neuronal stimulation significantly increases the release of mutant hTau, whereas wild-type hTau is unaffected. Importantly, BoNT/A blocks mutant hTau release, indicating that this process is modulated by SNAP25 in intact neurons. These results suggest that BoNTs are potent tools to study the spreading of pathological proteins in neurodegenerative diseases and will play a central role in identifying novel molecular targets for the development of therapeutic interventions to treat tauopathies.

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Section: Discussionmentioning

confidence: 99%

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

Panzi

Lazo²,

Surana

et al. 2023

Preprint

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“…If the amount of the bonded albumin to the mycotoxin is high in the circulation, the displacement may lead to significant changes in its distribution and/or removal of tissue, resulting in toxicity. Moreover, the species differences in albumin binding can help to understand how the toxicity of some mycotoxins (e. g., zearalenone and its metabolites) changes [9,10] …”

Section: Introductionmentioning

confidence: 99%

“…Moreover, the species differences in albumin binding can help to understand how the toxicity of some mycotoxins (e. g., zearalenone and its metabolites) changes. [9,10] Optical spectrometer is considered as an important instrument to study how small ligands interact with biological molecules [11][12][13][14][15][16][17] and the binding parameters in spectroscopic methods play a major role in pharmacokinetics. [18][19][20][21] Among spectroscopic techniques, fluorescence and ultraviolet-visible (UV-Vis) spectroscopies are powerful to investigate proteinligand interactions.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Study of the Interaction between Ochratoxin A and Human Serum Albumin by Spectroscopic and Molecular Docking Methods

Vakili,

Baher,

Vaezi

et al. 2023

ChemistrySelect

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Ochratoxin A (OA) is a mycotoxin that has a potential risk to human health due to its nephrotoxic, immunotoxic and carcinogenic effects. For these reasons the interaction of ochratoxin A with human serum albumin (HSA) was investigated in physiological media by various techniques such as UV‐Vis, fluorescence (FL), circular dichroism (CD), attenuated total reflection (ATR), differential scanning calorimetry (DSC), atomic force microscopy (AFM) and molecular docking study via Auto Dock‐vina software. The fluorescence intensity of tryptophan in HSA was strongly quenched in the present of OA and the quenching constants and binding constant were valued 108 M−1 and 1.04 M−1, respectively. The CD spectra showed alteration in the secondary structure of HSA in the presence of ochratoxin by reducing the regular alpha helical structure and increasing the beta‐sheet structure. By increasing the concentration of OA to 1.25 μM, the intensity of absorption spectrum at 282 nm was increased, indicating the strong interaction of OA and HSA. The enthalpies of these molecular interaction calculated from DSC analysis indicate OA interaction with HAS is exothermic. The docking calculations showed that the amino acids of Lys190, ASP187, LYS519, ARG186 and ARG428 were interacted with OA by hydrogen bonding.

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AbobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA neurotoxin content and activity: potential implications for duration of efficacy in patients

Cited by 2 publications

References 0 publications

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

Botulinum neurotoxin A modulates the axonal release of pathological tau in hippocampal neurons

In Vitro Study of the Interaction between Ochratoxin A and Human Serum Albumin by Spectroscopic and Molecular Docking Methods

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