A5086779872- Botulinum Toxin and Related Neurological Disorders
- Receptor Mechanisms and Signaling
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- Nerve injury and regeneration
- Clostridium difficile and Clostridium perfringens research
- Hereditary Neurological Disorders
- Neural dynamics and brain function
- Wnt/β-catenin signaling in development and cancer
- RNA Research and Splicing
- Ion channel regulation and function
- Neuroinflammation and Neurodegeneration Mechanisms
- Neurogenesis and neuroplasticity mechanisms
- Pain Mechanisms and Treatments
- Diphtheria, Corynebacterium, and Tetanus
- Neurological disorders and treatments
- Toxin Mechanisms and Immunotoxins
King's College London
2018-2022
Medical Research Council
2019-2022
HUN-REN Institute of Experimental Medicine
2010-2019
Hungarian Academy of Sciences
2010-2019
University College London
2014-2015
Cancer Research UK
2012-2015
The Honourable Society of Lincoln's Inn
2012
The striking differences between the clinical symptoms of tetanus and botulism have been ascribed to different fate parental neurotoxins once internalised in motor neurons. Tetanus toxin (TeNT) is known undergo transcytosis into inhibitory interneurons block release neurotransmitters spinal cord, causing a spastic paralysis. In contrast, botulinum (BoNTs) acetylcholine at neuromuscular junction, therefore inducing flaccid Whilst overt experimental evidence supports sorting TeNT axonal...
Tetanus neurotoxin (TeNT) is among the most poisonous substances on Earth and a major cause of neonatal death in nonvaccinated areas. TeNT targets neuromuscular junction (NMJ) with high affinity, yet nature receptor complex remains unknown. Here, we show that presence nidogens (also known as entactins) at NMJ main determinant for binding. Inhibition TeNT-nidogen interaction by using small nidogen-derived peptides or genetic ablation prevented binding to neurons protected mice from...
Significance Brain function requires appropriate numbers of different neuronal subtypes, but how these are established remains poorly understood. Here, we identified a key role for the cerebral cortex in remotely controlling interneuron survival and thus establishing two main types interneurons another brain region, striatum. While cortical pyramidal cells directly control parvalbumin-expressing GABAergic neurons, cholinergic is indirectly controlled through activity striatal medium spiny...
Abstract The type II classic cadherin subfamily contains a number of extensively studied genes ( cdh6, cdh8, cdh11 ); however, the expression and function other members have only been partially described. Here we employed reverse‐transcription polymerase chain reaction (RT‐PCR) in situ hybridization to characterize cortical hippocampal all cadherins (with exception nonneural Cdh5 ) developing adult mouse brain. Many these ubiquitous mRNA distribution patterns throughout development,...
The multiplex role of cadherin-based adhesion complexes during development pallial excitatory neurons has been thoroughly characterized. In contrast, much less is known about their function interneuron development. Here, we report that conditional removal N-cadherin (Cdh2) from postmitotic neuroblasts the subpallium results in a decreased number Gad65-GFP-positive interneurons adult cortex. We also found precursor migration into pallium was already delayed at E14. Using immunohistochemistry...
The assembly of functional neuronal circuits requires appropriate numbers distinct classes neurons, but the mechanisms through which their relative proportions are established remain poorly defined. Investigating mouse striatum, here we found that two most prominent subtypes striatal interneurons, parvalbumin-expressing (PV+) GABAergic and cholinergic (ChAT+) undergo extensive programmed cell death between first second postnatal weeks. Remarkably, survival PV+ ChAT+ interneurons is regulated...