A5080245027- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Chronic Lymphocytic Leukemia Research
- Chronic Myeloid Leukemia Treatments
- Cellular transport and secretion
- E-Government and Public Services
- ICT Impact and Policies
- Polyomavirus and related diseases
- Drug Transport and Resistance Mechanisms
- Cholinesterase and Neurodegenerative Diseases
- Lung Cancer Treatments and Mutations
- Systemic Sclerosis and Related Diseases
- Photoreceptor and optogenetics research
- Lipid Membrane Structure and Behavior
- Adenosine and Purinergic Signaling
- Neuroinflammation and Neurodegeneration Mechanisms
- Pharmaceutical studies and practices
- Cancer Mechanisms and Therapy
- Protein Kinase Regulation and GTPase Signaling
- Vector-Borne Animal Diseases
- Local Government Finance and Decentralization
- T-cell and Retrovirus Studies
- Neurotransmitter Receptor Influence on Behavior
- Multiple Sclerosis Research Studies
Sanofi (United States)
2017-2024
Sanofi (France)
2023
University of Mississippi Medical Center
2023
National Institutes of Health
2021
National Institute of Neurological Disorders and Stroke
2021
AVEO Oncology (United States)
2019
Synthetic Biologics (United States)
2018
Kookmin University
2018
UNSW Sydney
2008-2017
University of Canberra
2017
Inositol 1,4,5-trisphosphate (IP 3 )-induced calcium release from intracellular stores is a regulator of cytosolic-free levels. The subsecond kinetics and regulation IP -induced calcium-45 synaptosome-derived microsomal vesicles were resolved by rapid superfusion. Extravesicular acted as coagonist, potentiating the transient calcium-45. Thus, elevation cytosolic levels may trigger in vivo. also produced more slowly developing, reversible inhibition release. Sequential positive negative...
Presynaptic calcium channels are crucial elements of neuronal excitation-secretion coupling. In mammalian brain, they have been difficult to characterize because most presynaptic terminals too small probe with electrodes, and available pharmacological tools such as dihydropyridines omega-conotoxin largely ineffective. Subsecond measurements synaptosomal glutamate release now used assess channel activity in order study the action peptide toxins from venom funnel web spider Agelenopsis aperta,...
The regulation of excitation-secretion coupling by Ca2+ channels is a fundamental property the nerve terminal. Peptide toxins that block specific channel types have been used to identify which participate in neurotransmitter release. Subsecond measurements [3H]-glutamate and [3H]dopamine release from rat striatal synaptosomes showed P-type channels, are sensitive Agelenopsis aperta venom peptide omega-Aga-IVA, trigger both transmitters. Dopamine (but not glutamate) was also controlled...
Rat brain synaptosomes are shown to contain functional voltage- sensitive Ca2+ channels that inhibited by organic channel blockers. Depolarization of with high K+ stimulates uptake 45Ca2+ which is biphasic in its time course. Replacement external Na+ choline eliminates the slower phase depolarization- stimulated uptake, leaving only a rapid process terminates within 1 sec. This rapid, tetrodotoxin-insensitive can be inactivated prior depolarization synaptosomes. has no effect on rate...
Inhibition of a mitochondrial enzyme during multiple sclerosis treatment modulates antigen-specific T cell responses in an affinity-dependent fashion.
Tolebrutinib is a covalent BTK inhibitor designed and selected for potency CNS exposure to optimize impact on BTK-dependent signaling in CNS-resident cells. We applied translational approach evaluate three inhibitors Phase 3 clinical development MS with respect their relative block the METHODS: used vitro kinase cellular activation assays, alongside pharmacokinetic sampling of cerebrospinal fluid (CSF) non-human primate cynomolgus estimate ability these candidates (evobrutinib, fenebrutinib,...
Interleukin-1 (IL-1), a cytokine involved in the acute phase reaction to injury and infection, has multiple effects central nervous system, including induction of fever sleep release several neuropeptides. We evaluated IL-1 beta on inhibitory postsynaptic function at gamma-aminobutyric acidA (GABAA) receptor. (100 pg/ml 10 ng/ml) augmented GABAA receptor cortical synaptic preparations. This effect was largely prevented by incubation with specific antagonist. The related cytokines...
Throughout the course of multiple sclerosis, gradually progressive neurologic impairment can occur, which has been called disability accrual. Current disease-modifying therapies for sclerosis have limited effects on accrual unrelated to relapses, is thought be partially caused by chronic, nonresolving neuroinflammation within central nervous system. Tolebrutinib an oral, brain-penetrant Bruton's tyrosine kinase inhibitor that targets myeloid cells (including microglia) and B in both...
Tolebrutinib is an oral, brain-penetrant, and bioactive Bruton's tyrosine kinase inhibitor that modulates peripheral inflammation persistent immune activation within the central nervous system, including disease-associated microglia B cells. More data are needed on its efficacy safety in treating relapsing multiple sclerosis. In two phase 3, double-blind, double-dummy, event-driven trials (GEMINI 1 GEMINI 2), participants with sclerosis were randomly assigned a 1:1 ratio to receive...
The Ral proteins are members of the Ras superfamily GTPases. Because they reside in synaptic vesicles, we used transgenic mice expressing a dominant inhibitory form to investigate role neurosecretion. Using synaptosomal secretion assay, found that while K(+)-evoked glutamate was normal, protein kinase C-mediated enhancement suppressed mutant mice. Since C effects on have been shown be due size readily releasable pool vesicles docked at plasma membrane, directly measured refilling this after...
The regulation of the inositol 1,4,5-trisphosphate (IP3) receptor in liver was analyzed using a novel superfusion method. Hepatic microsomes were loaded with 45Ca2+, and superfused at high flow rates to provide precise control over IP3 Ca2+ concentrations ([Ca2+]) isolate 45Ca2+ release from reuptake. dependent on both [Ca2+] IP3. initial rate biphasic function [Ca2+], increasing as approached 3 μM but decreasing higher concentrations, suggesting that hepatic is regulated by two sites,...
A major factor underlying compulsive tobacco use is nicotine-induced modulation of dopamine release in the mesolimbic reward pathway (Wise and Rompre, 1989). An established biochemical mechanism for nicotine-enhanced by activating presynaptic nicotinic acetylcholine receptors (nAChRs) (Wonnacott, 1997). Prolonged application 10 -7 to -5 m nicotine striatal synaptosomes promoted a sustained efflux [ 3 H]dopamine. This effect was mediated non-α7 nAChRs, because it blocked 5 μ mecamylamine but...
Tottering, a mouse model for absence epilepsy and cerebellar ataxia, carries mutation in the gene encoding class A (P/Q-type) Ca2+ channels, dominant exocytotic channel at most synapses mammalian central nervous system. Comparing tottering to wild-type mice, we have studied glutamatergic transmission between parallel fibres Purkinje cells slices. Results from biochemical assays electrical field recordings demonstrate that glutamate release fibre terminals of is controlled largely by B...