Differential endopeptidase activity of different forms of type A botulinum neurotoxin: A unique relationship between the size of the substrate and activity of the enzyme

Ambrin, Ghuncha; Kumar, Raj; Singh, Bal Ram

doi:10.1016/j.toxicon.2017.12.055

Cited by 3 publications

(2 citation statements)

References 28 publications

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“…As the physiology of the in vitro model is different from the human model, it is difficult to determine the duration of treatment and the concentration, given the complexity of the human body. 50 n m and higher concentration of BoNT/A has been used in vitro models for determining the endopeptidase activity [ 50 ] with incubation time, varying up to 96 h. [ 51 ] To mimic the BoNT/A dosage, we monitored the cell viability as the deciding factor for determining the treatment duration.…”

Section: Discussionmentioning

confidence: 99%

“…Further investigation is important to correlate the form of toxin and its potentially damaging effects. If these differences are due to the size [ 50 ] or structural differences between the two proteins or if NAPs play an additional role in modulating a change in response, and would these differences mediate cytotoxicity, neurodegeneration, or asymptomatic condition, is yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Ambrin,

Kang,

Van Do

et al. 2024

Advanced Science

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Botulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi‐dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi‐dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron‐glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1β, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A‐treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Ambrin,

Kang,

Van Do

et al. 2024

Advanced Science

Self Cite

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Recent progress in optical and electrochemical biosensors for sensing of Clostridium botulinum neurotoxin

Eivazzadeh‐Keihan

Pashazadeh-Panahi

Baradaran

et al. 2018

TrAC Trends in Analytical Chemistry

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Current Developments in Diagnostic Assays for Laboratory Confirmation and Investigation of Botulism

2022

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Detection of botulinum neurotoxin or isolation of the toxin producing organism is required for the laboratory confirmation of botulism in clinical specimens. In an effort to reduce animal testing required by the gold standard method of botulinum neurotoxin detection, the mouse bioassay, many technologies have been developed to detect and characterize the causative agent of botulism. Recent advancements in these technologies have led to improvements in technical performance of diagnostic assays; however, many emerging assays have not been validated for the detection of all serotypes in complex clinical and environmental matrices. Improvements to culture protocols, endopeptidase-based assays, and a variety of immunological and molecular methods have provided laboratories with a variety of testing options to evaluate and incorporate into their testing algorithms. While significant advances have been made to improve these assays, additional work is necessary to evaluate these methods in various clinical matrices and to establish standardized criteria for data analysis and interpretation.

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Differential endopeptidase activity of different forms of type A botulinum neurotoxin: A unique relationship between the size of the substrate and activity of the enzyme

Cited by 3 publications

References 28 publications

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Recent progress in optical and electrochemical biosensors for sensing of Clostridium botulinum neurotoxin

Current Developments in Diagnostic Assays for Laboratory Confirmation and Investigation of Botulism

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