A5051509408- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Receptor Mechanisms and Signaling
- Insect and Pesticide Research
- Venomous Animal Envenomation and Studies
- Crystallization and Solubility Studies
- Healthcare and Venom Research
- Epilepsy research and treatment
- X-ray Diffraction in Crystallography
- Amino Acid Enzymes and Metabolism
- Cholinesterase and Neurodegenerative Diseases
- Molecular Sensors and Ion Detection
- Chemical Synthesis and Analysis
- Neurotransmitter Receptor Influence on Behavior
- Insect and Arachnid Ecology and Behavior
- Pharmacological Effects and Toxicity Studies
- Drug Transport and Resistance Mechanisms
- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Blood properties and coagulation
- Erythrocyte Function and Pathophysiology
- Hemoglobin structure and function
- Natural product bioactivities and synthesis
- Synthesis of Indole Derivatives
Drexel University
2015-2025
University of Pittsburgh
2004-2009
Vollum Institute
2002-2004
Oregon Health & Science University
2003-2004
Howard Hughes Medical Institute
2002-2003
Universidade de São Paulo
2000-2003
University Hospital of Zurich
1994
Macrophages have been found to release glutamate and thereby induce neuronal cell death by excitotoxicity, a mechanism that seems be operative in various neurologic diseases. In this study, it is shown the presence of both cystine glutamine culture medium indispensable for brain macrophages cause death. Furthermore, requires protein synthesis since cycloheximide prevented accumulation neurotoxic molecule supernatants microglial cultures. Aminoadipate, which was inhibit uptake system xc-...
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis various neurological disorders, such as stroke, brain trauma, epilepsy, and neurodegenerative diseases, among others. EAAT2 is main subtype responsible for glutamate clearance brain, having a key role regulating transmission preventing excitotoxicity. Therefore, compounds that increase expression or activity have therapeutic potential neuroprotection. Previous studies identified molecular...
Previous studies have shown that a compound purified from the spider <i>Parawixia bistriata</i> venom stimulates activity of glial glutamate transporters and can protect retinal tissue ischemic damage. To understand mechanism by which this enhances transport, we examined its effects on functional properties after solubilization reconstitution in liposomes transfected COS-7 cells. Here, demonstrate both systems Parawixin1 promotes direct selective enhancement influx EAAT2 transporter subtype...
Excitatory amino acid transporters (EAATs) are essential CNS proteins that regulate glutamate levels. Excess release and alteration in EAAT expression associated with several disorders. Previously, we identified positive allosteric modulators (PAM) of EAAT2, the main transporter, have demonstrated their neuroprotective properties vitro. Herein, report on structure–activity relationships (SAR) for analogs from virtual screening our medicinal chemistry campaign. This work selective EAAT2...
(1) In this study, we examined the effects of crude venom from spider Parawixia bistriata on glutamate and GABA uptake into synaptosomes prepared rat cerebral cortex. Addition to cortical stimulated inhibited in a concentration-dependent manner. (2) The was fractionated using reverse-phase high-performance liquid chromatography preparative column. fraction that retained uptake-stimulating activity further purified analytical column followed by ion-exchange chromatography. (3) active...
Dysfunction of excitatory amino acid transporters (EAATs) has been implicated in the pathogenesis various neurological disorders, such as stroke, brain trauma, epilepsy, and several neurodegenerative disorders. EAAT2 is main transporter subtype responsible for glutamate clearance brain, plays a key role regulating neurotransmission preventing excitotoxicity. Therefore, compounds that increase activity have therapeutic potential neuroprotection. In previous studies, we used virtual screening...
Traumatic brain injury (TBI) in humans and animals leads to an acute sustained increase tissue glutamate concentrations within the brain, triggering glutamate-mediated excitotoxicity. Excitatory amino acid transporters (EAATs) are responsible for maintaining extracellular central nervous system below neurotoxic levels. Our results demonstrate that as early 5 min up 2 h following trauma brain-injured rats, activity (Vmax) of EAAT2 cortex hippocampus was significantly decreased, compared with...
(R)-7 [(R)-AS-1] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between CNS-related adverse effects was also observed. In vitro studies with primary glia cultures COS-7 cells expressing the glutamate transporter EAAT2 enhancement of uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular...
The dopamine transporter (DAT) serves a pivotal role in controlling (DA)-mediated neurotransmission by clearing DA from synaptic and perisynaptic spaces its action at postsynaptic receptors. Major drugs of abuse such as amphetamine cocaine interact with DAT to mediate their effects enhancing extracellular concentrations. We previously identified novel allosteric site the related human serotonin that lies outside central substrate inhibitor binding pocket. used hybrid structure based (HSB)...
The neurotransmitter transporters of the SLC6 family play critical roles in regulation neurotransmission and are primary targets therapeutic agents used to treat clinical disorders involving compromised signaling. dopamine norepinephrine have been implicated such as attention deficit hyperactivity disorder (ADHD) substance abuse. GABA (GATs) serve a target for anxiolytic, antidepressant, antiepileptic therapies. In this work, interaction with was characterized derivative lignan (−)-cubebin...
The major contribution of this work is the isolation a neuroprotective compound referred to as 2-amino-5-ureidopentanamide (FrPbAII) (M(r) = 174) from Parawixia bistriata spider venom and an investigation its mode action. FrPbAII inhibits synaptosomal GABA uptake in dose-dependent manner probably does not act on Na(+), K(+), Ca(2+) channels, GABA(B) receptors, or gamma-aminobutyrate:alpha-ketoglutarate aminotransferase enzyme; therefore, it directly dependent these structures for Direct...
Abstract Excitatory amino acid transporters ( EAAT s) regulate glutamatergic signal transmission by clearing extracellular glutamate. Dysfunction of these has been implicated in the pathogenesis various neurological disorders. Previous studies have shown that venom from spider Parawixia bistriata and a purified compound (Parawixin1) stimulate 2 activity protect retinal tissue ischemic damage. In present study, subtype specificity this was explored, employing chimeric proteins between 3...
In this article we describe an in vivo anticonvulsant effect from denatured crude venom and partially isolated fractions two spiders: Parawixia bistriata Scaptocosa raptoria. Intracerebroventricular injections of these venoms abolished rat convulsive tonic-clonic seizures induced by picrotoxin, bicuculline pentylenetetrazole, also, inhibited GABA uptake synaptosomes cerebral cortex. The described work seems to be promising tools for the study GABAergic system, may a potential source new drugs.