A5034305626- Botulinum Toxin and Related Neurological Disorders
- Nerve injury and regeneration
- Signaling Pathways in Disease
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Lipid Membrane Structure and Behavior
- Ion channel regulation and function
- Neurogenesis and neuroplasticity mechanisms
- Cellular transport and secretion
- Neurotransmitter Receptor Influence on Behavior
- Endoplasmic Reticulum Stress and Disease
- Erythrocyte Function and Pathophysiology
- Neurological disorders and treatments
- Pain Mechanisms and Treatments
- RNA regulation and disease
- Biochemical and Structural Characterization
- Protein Kinase Regulation and GTPase Signaling
- Plant-based Medicinal Research
- Amyotrophic Lateral Sclerosis Research
- Retinoids in leukemia and cellular processes
- Alzheimer's disease research and treatments
- Venomous Animal Envenomation and Studies
- Sphingolipid Metabolism and Signaling
- Toxin Mechanisms and Immunotoxins
- Neuroinflammation and Neurodegeneration Mechanisms
Hospital Universitario Araba
2024
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2022
Universitat Autònoma de Barcelona
2011-2022
Centro de Investigación Biomédica en Red
2016-2021
Howard University
2016
Instituto Cajal
2016
Consejo Superior de Investigaciones Científicas
2016
St. Paul's Hospital
2012
Maastricht University
2012
Fresenius Medical Care (Germany)
2012
The C-terminal domain of the heavy chain tetanus toxin (Hc-TeTx) is a nontoxic peptide with demonstrated in vitro and vivo neuroprotective effects against striatal dopaminergic damage induced by 1-methyl-4-phenylpyridinium 6-hydoxydopamine, suggesting its possible therapeutic potential Parkinson's disease. Methamphetamine, widely abused psychostimulant, has selective neurotoxicity rodents, monkeys, humans. This study was undertaken to determine whether Hc-TeTx might also protect...
Previous publications from our group [Gil, Chaib, Pelliccioni and Aguilera (2000) FEBS Lett. 481, 177-182; Gil, Blasi (2001) Biochem. J. 356, 97-103] have reported the activation, in rat brain synaptosomes, of several phosphoproteins, such as neurotrophin tyrosine kinase (Trk) A receptor, phospholipase Cgamma-1, protein C (PKC) isoforms extracellular-signal-regulated kinases 1 2 (ERK-1/2). In present study, we examined, by means phospho-specific antibodies, activation signalling cascades...
When cultured cerebellar granule neurones are transferred from a medium containing high extracellular potassium concentration ([K+]e) (25 mm) to one with lower [K+]e (5 mm), caspase-3 activity is induced and cells die apoptotically. In contrast, if in non-depolarizing conditions treated brain-derived neurotrophic factor (BDNF), activity, chromatin condensation cell death markedly diminished. this study, we show that the C-terminal domain of tetanus toxin heavy-chain (Hc-TeTx) able produce...
Abstract: Complete obstruction of the maternal blood flow to fetal rats at 20 days gestation for a period 10 min causes significant shift ∼22% in protein kinase C (PKC) activity from cytosolic membrane‐bound form brain. This translocation can be entirely reversed without losses by single intraperitoneal injection into gravid rat either mixture disialo‐ and trisialoganglioside [polysialoganglioside (PSG)] or GM1 (50 mg/kg body weight) given 3 h before onset ischemic episode. Cessation 15...
Abstract The C‐terminal domain of tetanus toxin (Hc‐TeTx) has been suggested to act as a neuroprotective agent by activating signaling pathways related neurotrophins and also exert anti‐apoptotic effects. Here, we show the beneficial properties recombinant protein Hc‐TeTx protect spinal motoneurons against excitotoxic damage. In vitro cord organotypic cultures were used assess acute glutamate Our results indicate that treatment improves motoneuron survival within short therapeutical window...
Previous reports have demonstrated that tetanus toxin (TeTx) induces activation and down‐regulation of protein kinase C (PKC). In the present work differential PKC isoforms signal transduction pathways, including nerve growth factor receptor trkA, phospholipase Cγ‐1 (PLCγ‐1), extracellular regulated kinases 1 2 (ERK‐1/2) by TeTx in a synaptosome‐enriched P fraction from rat brain is reported. clear translocation soluble (cytosolic) compartment to particulate (membranous) PKC‐β, ‐γ ‐δ...
A recent report [Gil, Chaib-Oukadour, Pelliccioni and Aguilera (2000) FEBS Lett. 481, 177-182] describes activation of signal transduction pathways by tetanus toxin (TeTx), a Zn(2+)-dependent endopeptidase synthesized the Clostridium tetani bacillus, which is responsible for disease. In present work, specific protein kinase C (PKC) isoforms intracellular signal-transduction pathways, include nerve-growth-factor (NGF) receptor trkA, phospholipase C(PLC)gamma-1 extracellular regulated kinases...
Abstract: Clostridium neurotoxins produce inhibition of both basal and K + ‐evoked serotonin release in rat brain synaptosomes. To these effects, tetanus toxin (TeTx), as well botulinum neurotoxin type A (BoNT/A), added to synaptosomes, must be incubated at 37°C over a long interval (hours). This exocytosis was abolished with previous treatment specific Zn 2+ ‐metalloprotease inhibitors. Nevertheless, short incubation time produces different behavior the indicated neurotoxins: TeTx...
Abstract: A single intraventricular injection into adult rats of 100 mouse lethal doses tetanus toxin (TeTox) produces a marked intracellular redistribution Ca 2+ /phosphatidylserine (PtdSer)‐dependent protein kinase C (PKC) activity. Changes are particularly pronounced in hypothalamus, hippocampus, and spinal cord structures. Translocation PKC from the inactive cytosolic compartment to membrane‐bound active form is followed by time‐dependent reduction both total activity enzyme protein. The...
Protein ectodomain shedding is the proteolytic release of extracellular domain membrane‐bound proteins. Neurotrophin receptor p75 NTR known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that detergent‐resistant membranes (DRM), also as lipid rafts, only its full‐length form. Disrupting integrity rafts causes solubilization after detergent treatment and enhancement Analyses enzymes described being responsible for shedding, i.e. tumor necrosis...
Neurotrophins are a group of secreted polypeptides, which comprises Nerve Growth Factor (NGF) and Brain‐Derived Neurotrophic (BDNF). Each neurotrophin can bind specifically to tyrosine kinase Trk receptor (TrkA, TrkB or TrkC), while all the neurotrophins bind, with similar affinity, p75 (p75 NTR ). Experiments on cell viability promotion by BDNF in granule neurons NGF PC12 cells show that neurotrophin‐exerted is neutral sphingomyelinase (nSMase)‐dependent, since GW4869 siRNA knockdown...