Botulinum neurotoxins (BoNTs), the causative agent of human botulism, are the most potent naturally occurring toxins known. BoNT/A1, the most studied BoNT, is also used as an important biopharmaceutical. In this study, the biological activity of BoNT/A1 is compared to that of BoNT/A2 using neuronal cell models. The data obtained indicate faster and increased intoxication of neuronal cells by BoNT/A2 than BoNT/A1, and that the mechanism underlying this increased toxicity is faster and more efficient cell entry that is independent of ganglioside binding. These results have important implications for the development of new BoNT based therapeutics and BoNT countermeasures.
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http://dx.doi.org/10.1016/j.febslet.2010.11.045 | DOI Listing |
Front Mol Neurosci
January 2025
Neuroscience Center, HiLIFE, University of Helsinki, Helsinki, Finland.
Introduction: The neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.
View Article and Find Full Text PDFFront Pharmacol
January 2025
Department of Neuroscience, Washington University in St. Louis, St. Louis, MO, United States.
The Kv3.2 subfamily of voltage activated potassium channels encoded by the gene is abundantly expressed in neurons that fire trains of fast action potentials that are a major source of cortical inhibition. Gain-of-function (GOF) pathogenic variants in and , encoding Kv3.
View Article and Find Full Text PDFFront Comput Neurosci
January 2025
Institute for Neural Computation, Faculty of Computer Science, Ruhr University Bochum, Bochum, Germany.
Introduction: The hippocampal formation exhibits complex and context-dependent activity patterns and dynamics, e.g., place cell activity during spatial navigation in rodents or remapping of place fields when the animal switches between contexts.
View Article and Find Full Text PDFBrain Behav Immun Health
December 2024
James & Lillian Martin Centre, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic. After the success of therapeutics and worldwide vaccination, the long-term sequelae of SARS-CoV-2 infections are yet to be determined. Common symptoms of COVID-19 include the loss of taste and smell, suggesting SARS-CoV-2 infection has a potentially detrimental effect on neurons within the olfactory/taste pathways, with direct access to the central nervous system (CNS).
View Article and Find Full Text PDFFront Neurosci
January 2025
Division of Medical Sciences, University of Victoria, Victoria, BC, Canada.
The vagus nerve (VN) is the primary parasympathetic nerve, providing two-way communication between the body and brain through a network of afferent and efferent fibers. Evidence suggests that altered VN signaling is linked to changes in the neuroimmune system, including microglia. Dysfunction of microglia, the resident innate immune cells of the brain, is associated with various neurodevelopmental disorders, including schizophrenia, attention deficit hyperactive disorder (ADHD), autism spectrum disorder (ASD), and epilepsy.
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