A5076983407- Toxin Mechanisms and Immunotoxins
- Neuroscience and Neuropharmacology Research
- Neuropeptides and Animal Physiology
- Alzheimer's disease research and treatments
- Polyamine Metabolism and Applications
- Receptor Mechanisms and Signaling
- Pharmacological Receptor Mechanisms and Effects
- Peptidase Inhibition and Analysis
- Ion channel regulation and function
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Pain Mechanisms and Treatments
- Signaling Pathways in Disease
- Neurotransmitter Receptor Influence on Behavior
- Genetic Neurodegenerative Diseases
- Nerve injury and regeneration
- Galectins and Cancer Biology
- Neurogenesis and neuroplasticity mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Psychedelics and Drug Studies
- Nicotinic Acetylcholine Receptors Study
- Thermoregulation and physiological responses
- Blood properties and coagulation
- Epilepsy research and treatment
- Ocular Surface and Contact Lens
Bicycle Therapeutics (United Kingdom)
2020-2025
Neurology, Inc
2025
Pfizer (United Kingdom)
2018
Allen Institute for Brain Science
2008
MSD (UK) Limited (United Kingdom)
1993-2006
Merck & Co., Inc., Rahway, NJ, USA (United States)
1993-2005
At Bristol
1991
Papouch (Czechia)
1991
King's College Hospital
1991
High frequency oscillations (HFOs) >200 Hz are believed to be associated with epileptic processes. The spatial distribution of HFOs and their evolution over time leading up seizure onset is unknown. Also, recording through conventional intracranial electrodes not well established. We therefore wished determine whether could recorded using commercially available depth macroelectrodes. also examined the temporal progression during transition activity.Intracranial electroencephalography (EEG)...
Abstract Multiple tumor types overexpress Nectin-4 and the antibody–drug conjugate (ADC), enfortumab vedotin (EV) shows striking efficacy in clinical trials for metastatic urothelial cancer, which expresses high levels of Nectin-4, validating as a target toxin delivery this indication. Despite excellent data little are reported EV other expressing tumors therapy can produce significant toxicities many patients, frequently leading to discontinuation treatment. Thus, additional approaches with...
N‐methyl‐ d ‐aspartate (NMDA) receptor ion channel antagonists have been reported to cause pronounced increases in cerebral glucose metabolism (CMR glc ) and transient reversible vacuolation within pyramidal cortical neurones. The present studies examined rats the effects of NMDA antagonist, L‐687,414 ( R ‐(+)‐ cis ‐4‐methyl‐3‐amino‐l‐hydroxypyrolid‐2‐one; (+)‐ ‐4‐methyl‐HA‐966) on regional CMR neuronal morphology. was given as a steady state intravenous infusion for 4 h neuroprotective dose...
Substance P receptor [neurokinin 1 (NK1] antagonists (SPAs) represent a novel mechanistic approach to antidepressant therapy with comparable clinical efficacy selective serotonin reuptake inhibitors (SSRIs). Because SSRIs are thought exert their therapeutic effects by enhancing central serotonergic function, we have examined whether SPAs regulate neuronal activity in the dorsal raphe nucleus (DRN), main source of projections forebrain. Using vivo electrophysiological techniques guinea pig,...
Abstract Marked species differences in the distribution of central tachykinin receptors are reported but uncertainty remains about ability available ligands to detect NK 2 and 3 human brain. We compared 1 , sections from rodent, primate, brain using 125 I‐labeled substance P (SP) for receptor, neurokinin A (NKA) B (NKB) eledoisin receptors. Duration exposure autoradiographic film was 7 days [ I]SP up 90 other ligands. High levels specific binding were seen throughout brains all studied....
The putative cache (Ca 2+ channel and chemotaxis receptor) domain containing 1 (CACHD1) protein has predicted structural similarities to members of the α2δ voltage-gated Ca auxiliary subunit family. CACHD1 mRNA were highly expressed in male mammalian CNS, particular thalamus, hippocampus, cerebellum, with a broadly similar tissue distribution V 3 subunits, 3.1. In expression studies, increased cell-surface localization 3.1, these proteins close proximity at cell surface, consistent formation...
Caspases, key enzymes in the apoptosis pathway, have been detected brain of HD patients and animal models disease. In present study, we investigated neuroprotective properties a new, reversible, caspase‐3‐specific inhibitor, M826 (3‐({(2 S )‐2‐[5‐ tert ‐butyl‐3‐{[(4‐methyl‐1,2,5‐oxadiazol‐3‐yl)methyl]amino}‐2‐oxopyrazin‐1(2 H )‐yl]butanoyl}amino)‐5‐[hexyl(methyl)amino]‐4‐oxopentanoic acid), rat malonate model HD. Pharmacokinetic autoradiography studies after intrastriatal (i.str.) injection...
Improving the delivery of antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) to skeletal cardiac muscles remains a pivotal task toward broader application oligonucleotide therapeutics. The targeting myofibers cardiomyocytes via conjugation ASOs siRNAs ligands that bind human transferrin receptor 1 (TfR1) has gathered significant interest in recent years. However, selection with low molecular weight optimal biophysical binding properties is crucial maximize potential TfR1...
EDG receptors are a family of closely related G-protein-coupled receptors, so-called since the first member to be cloned is encoded by an endothelial differentiation gene. Of six members identified, five use lysophospholipids as their endogenous ligands. The sixth receptor, EDG-6, remains orphan. These activate multiple secondary-messenger pathways involving coupling Gi, Gq/11, and G12/13 trimeric guanine nucleotide-binding proteins thought play important role in cell growth, development...
The current study examined the long-term effect of brief exposure to 3,4-methylenedioxymethamphetamine (MDMA) on local cerebral glucose utilization (LCGU) in specific brain regions immediately following administration 5-HT2A/2C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Wistar rats (post-natal day (PND) 28, n = 24) were administered MDMA (5 mg/kg, i.p.) or saline (1 ml/kg, four times daily for 2 consecutive days and core body temperature was recorded. Fifty-five...
We have studied by in situ hybridization histochemistry the mRNA expression of c-fos immediate early gene brains wild type and dwarf(dw/dw) little(lit/lit) mutant mice after systemic injections synthetic GH secretagogues GHRP-6 L-163,191. Both induced a marked arcuate-ventromedial hypothalamus (ARC-VMH) both control indicating possible action on growth hormone releasing (GHRH) neurones ARC-VMH. dw/dw lit/lit showed 5-fold elevation GHRH ARC-VMH compared with animals under basal conditions....
Abstract Small molecule toxin conjugates offer a novel approach to tumor antigen specific targeting, allowing reduced systemic exposures and efficient penetration of cytotoxic payloads, compared large antibody conjugates. BT8009 is Bicycle Toxin Conjugate (BTC®) in which Nectin-4 binding Bicycle® (bicyclic peptide) conjugated through an inert sarcosine spacer chain, cleavable linker, the antimitotic MMAE. Increased expression has been reported multiple types (including bladder, breast,...