A5029258341- Pain Mechanisms and Treatments
- Ion channel regulation and function
- Neuroscience and Neuropharmacology Research
- Nicotinic Acetylcholine Receptors Study
- Axon Guidance and Neuronal Signaling
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuropeptides and Animal Physiology
- Connexins and lens biology
- Cholinesterase and Neurodegenerative Diseases
- Chemical synthesis and alkaloids
- Neuroscience and Neural Engineering
- Angiogenesis and VEGF in Cancer
- Phytochemistry and Biological Activities
- Pharmacological Receptor Mechanisms and Effects
- Adenosine and Purinergic Signaling
- Cardiac Ischemia and Reperfusion
- Plant-based Medicinal Research
- Peripheral Neuropathies and Disorders
- Histone Deacetylase Inhibitors Research
- Stress Responses and Cortisol
- Biochemical effects in animals
- Pharmacological Effects of Natural Compounds
- Phosphodiesterase function and regulation
- Lymphatic System and Diseases
New York University
2022-2024
University of Arizona
2022-2024
University of Florida
2024
University of Copenhagen
2024
Florida College
2024
Instituto Politécnico Nacional
2014-2020
Center for Research and Advanced Studies of the National Polytechnic Institute
2013-2020
Osteoarthritis (OA) is a highly prevalent and disabling joint disease, characterized by pathological progressive deformation clinical symptoms of pain. Disease-modifying treatments remain unavailable, pain-mitigation often suboptimal, but recent studies suggest beneficial effects inhibition the voltage-gated sodium channel NaV1.7. We previously identified compound 194 as an indirect inhibitor NaV1.7 preventing SUMOylation NaV1.7-trafficking protein, collapsin response mediator protein 2....
Small molecules directly targeting the voltage-gated sodium channel (VGSC) Na
Transmembrane Ca v 2.2 (N-type) voltage-gated calcium channels are genetically and pharmacologically validated, clinically relevant pain targets. Clinical block of (e.g., with Prialt/Ziconotide) or indirect modulation [e.g., gabapentinoids such as Gabapentin (GBP)] mitigates chronic but is encumbered by side effects abuse liability. The cytosolic auxiliary subunit collapsin response mediator protein 2 (CRMP2) targets to the sensory neuron membrane regulates their function via an...
Abstract Dysregulation of voltage-gated sodium Na V 1.7 channels in sensory neurons contributes to chronic pain conditions, including trigeminal neuropathic pain. We previously reported that results part from increased SUMOylation collapsin response mediator protein 2 (CRMP2), leading an CRMP2/Na interaction and functional activity 1.7. Targeting this feed-forward regulation, we developed compound 194 , which inhibits CRMP2 mediated by the SUMO-conjugating enzyme Ubc9. further demonstrated...
Abstract Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that binds numerous ligands including vascular endothelial growth factor A (VEGFA). Binding of this ligand to NRP-1 and the co-receptor, tyrosine kinase receptor VEGFR2, elicits nociceptor sensitization resulting in pain through enhancement activity voltage-gated sodium calcium channels. We previously reported blocking interaction between VEGFA with Spike protein SARS-CoV-2 attenuates VEGFA-induced dorsal root ganglion (DRG)...
Oral cancer causes pain associated with progression. We report here that the function of Ca2+ channel ORAI1 is an important regulator oral pain. was highly expressed in tumor samples from patients cancer, and activation caused sustained influx human cells. RNA-seq analysis showed regulated many genes encoding markers such as metalloproteases (MMPs) modulators. Compared control cells, cells lacking formed smaller tumors elicited decreased allodynia when inoculated into mouse paws. Exposure...
Abstract Paraneoplastic neurological syndromes arise from autoimmune reactions against nervous system antigens due to a maladaptive immune response peripheral cancer. Patients with small cell lung carcinoma or malignant thymoma can develop an the CV2/collapsin mediator protein 5 (CRMP5) antigen. For reasons that are not understood, approximately 80% of patients experience painful neuropathies. Here, we investigated mechanisms underlying anti-CV2/CRMP5 autoantibodies (CV2/CRMP5-Abs)-related...
Postoperative pain occurs in as many 70% of surgeries performed worldwide. management still relies on opioids despite their negative consequences, resulting a public health crisis. Therefore, it is important to develop alternative therapies treat chronic pain. Natural products derived from medicinal plants are potential sources novel biologically active compounds for development safe analgesics. In this study, we screened library natural identify small molecules that target the activity...
Over the past three decades, there has been a significant growth in use of natural products, with approximately 80% individuals using them for some aspect primary healthcare. Our laboratories have identified and studied compounds analgesic effects from dry land plants or their associated fungus during ten years. Here, we isolated characterized thirteen betulin analogs fifteen betulinic acid capacity to prevent calcium influx brought on by depolarization sensory neurons. The vitro inhibition...
The voltage-gated sodium channel Na V 1.7 is an essential component of human pain signaling. Changes in trafficking are considered critical the development neuropathic pain. SUMOylation collapsin response mediator protein 2 (CRMP2) regulates membrane and function 1.7. Enhanced CRMP2 correlates with increased activity. Pharmacological genetic interventions that interfere rodents have been shown to reverse mechanical allodynia. Sentrin or SUMO-specific proteases (SENPs) vital for balancing...
Antagonists (e.g., Ziconotide, Gabapentin) of the CaV2.2 (N-type) calcium channels are used clinically as analgesics for chronic pain. However, their use is limited by narrow therapeutic windows, difficult dosing routes (Ziconotide), misuse and overdoses (Gabapentin), well a litany adverse effects. Expansion novel pain therapeutics may emerge from mechanism-based interrogation CaV2.2. Here we report identification C2230, an aryloxy-hydroxypropylamine, blocker. C2230 trapped stabilized...
Mono-(2-ethylhexyl) phthalate (MEHP) is one of the main active metabolites di-(2-ethylhexyl) (DEHP). In our previous works, by using rat and Drosophila models, we showed a disruption neural function due to DEHP. However, exact effects MEHP are still unclear. To explore on central nervous system, electrophysiological properties spontaneous action potential (sAP), mini-excitatory postsynaptic currents (mEPSCs), ion channels, including Na+, Ca2+, K+ channels from CA3 hippocampal neurons area...
T-type calcium channels activate in response to subthreshold membrane depolarizations and represent an important source of Ca2+ influx near the resting potential. These regulate neuronal excitability have been linked pain. For this reason, are suitable molecular targets for development new non-opioid analgesics. Our previous work identified analogue benzimidazolonepiperidine, 5bk, that preferentially inhibited CaV3.2 reversed mechanical allodynia. In study, we synthesized screened a small...
The voltage-gated sodium NaV1.7 channel sets the voltage threshold for electrogenesis. Mutation in gene encoding human (SCN9A) cause painful neuropathies or pain insensitivity. NaV1.7. In dorsal root ganglion (DRG) neurons, activity and trafficking of are regulated by auxiliary collapsin response mediator protein 2 (CRMP2). Specifically, preventing addition a small ubiquitin-like modifier (SUMO), E2 SUMO-conjugating enzyme Ubc9, at lysine-374 (K374) CRMP2 reduces activity. We previously...
In vivo activation of dopamine D3 receptors (D3Rs) depresses motor activity. D3Rs are widely expressed in subthalamic, striatal, and dendritic dopaminergic inputs into the substantia nigra pars reticulata (SNr). vitro studies showed that nigral modulate their neurotransmitter release; thus, it could be these changes levels modify discharge nigro-thalamic neurons and, therefore, behavior. To determine how responses correspond to responses, we examined effect intra-nigral systemic blockade...
Four new triterpenes, 25-dehydroxy-25-methoxyargentatin C (1), 20S-hydroxyargentatin (2), 20S-hydroxyisoargentatin (3), and 24-epi-argentatin (4), together with 10 known triterpenes (5-14) were isolated from the aerial parts of Parthenium incanum. The structures 1-4 elucidated by detailed analysis their spectroscopic data, compounds 5-14 identified comparison data those reported. Since argentatin (11) was found to exhibit antinociceptive activity decreasing excitability rat macaque dorsal...
Abstract Dopamine D 3 R are widely expressed in basal ganglia where interact with 1 R. potentiate cAMP accumulation and GABA release stimulated by striatonigral neurons through “atypical” signaling. During dopaminergic denervation, signaling changes to a “typical” which antagonizes the effects of R, mechanisms this switching unknown. nf splice variant regulates membrane anchorage function decreases denervation; thus, it is possible that correlates expression increases membranal mask atypical...
Background and purpose: Postoperative pain occurs in as many 70% of the over 230 million surgeries performed annually worldwide. management still relies on opioids despite their negative consequences, resulting a public health crisis. Therefore, it is utmost importance to develop alternative therapies treat chronic pain. Natural products derived from medicinal plants are potential sources novel biologically active compounds for development analgesics safe analgesics. Experimental approach:...
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