A5012031138- Pain Mechanisms and Treatments
- Axon Guidance and Neuronal Signaling
- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Nicotinic Acetylcholine Receptors Study
- Connexins and lens biology
- Neurofibromatosis and Schwannoma Cases
- Neuropeptides and Animal Physiology
- Cellular transport and secretion
- Cardiac electrophysiology and arrhythmias
- Signaling Pathways in Disease
- Hippo pathway signaling and YAP/TAZ
- Hereditary Neurological Disorders
- Lipid Membrane Structure and Behavior
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Neuroscience and Neural Engineering
- Nerve injury and regeneration
- Biochemical effects in animals
- Pain Management and Placebo Effect
- Ubiquitin and proteasome pathways
- Fibromyalgia and Chronic Fatigue Syndrome Research
- Botulinum Toxin and Related Neurological Disorders
- Genetics and Neurodevelopmental Disorders
University of Florida
2024-2025
Florida College
2024-2025
Manipal Academy of Higher Education
2025
Kasturba Medical College, Manipal
2025
Center for Innovation
2018-2024
University of Arizona
2014-2024
New York University
2022-2024
Neurosciences Institute
2011-2024
Technical University of Darmstadt
2024
University of Milan
2024
Abstract Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding 2's spike protein to host angiotensin-converting enzyme triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both and vascular endothelial growth factor-A (VEGF-A)—a pronociceptive angiogenic factor, bind NRP-1, we tested whether could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by NRP-1 inhibitor...
Human T lymphocytes express a Ca<sup>2+</sup>-activated K<sup>+</sup> current (IK), whose roles and regulation are poorly understood. We amplified hSK4 cDNA from human lymphoblasts, we showed that its biophysical pharmacological properties when stably expressed in Chinese hamster ovary cells were essentially identical to the native IK current. In activated mRNA increased 14.6-fold (Kv1.3 1.3-fold), with functional consequences. Proliferation was inhibited Kv1.3 blocked naive cells, but block...
Collapsin response mediator proteins (CRMPs) specify axon/dendrite fate and axonal growth of neurons through protein-protein interactions. Their functions in presynaptic biology remain unknown. Here, we identify the N-type Ca(2+) channel (CaV2.2) as a CRMP-2-interacting protein. CRMP-2 binds directly to CaV2.2 two regions: domain I-II intracellular loop distal C terminus. Both co-localize within sites hippocampal neurons. Overexpression protein fused enhanced green fluorescent caused...
Collapsin response mediator proteins (CRMPs) mediate signal transduction of neurite outgrowth and axonal guidance during neuronal development. Voltage-gated Ca(2+) channels interacting are essential in signaling synaptic transmission this period. We recently identified the presynaptic N-type voltage-gated channel (Cav2.2) as a CRMP-2-interacting partner. Here, we investigated effects functional association CRMP-2 with Cav2.2 sensory neurons. colocalized at immature synapses growth cones,...
Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking the voltage-gated channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for driven by hierarchical interactions with posttranslationally modified versions binding partner collapsin response mediator protein 2 (CRMP2). The described between CRMP2 was enhanced conjugation small ubiquitin-like modifier (SUMO) further controlled phosphorylation status CRMP2....
Multiple adverse events are associated with the use of morphine for treatment chronic non-cancer pain, including opioid-induced hyperalgesia (OIH). Mechanisms OIH independent opioid tolerance and may involve metabolite morphine-3-glucuronide (M3G). M3G exhibits limited affinity receptors no analgesic effect. Previous reports suggest that can act via Toll-like receptor 4 (TLR4)/myeloid differentiation protein-2 (MD-2) heterodimer in central nervous system to elicit pain.Immunoblot...
Abstract Phosphorylation of the α subunit translation initiation factor eIF2 at serine 51 (eIF2 P) is a master regulator cell adaptation to various forms stress with implications in antitumor treatments chemotherapeutic drugs. Herein, we demonstrate that genetic loss kinases PERK and GCN2 or impaired P by means renders immortalized mouse fibroblasts as well human tumor cells increasingly susceptible death oxidative stress. We also show facilitates Akt activation subjected insults. However,...
Abstract Treatments for chronic pain are inadequate, and new options needed. Nonpharmaceutical approaches especially attractive with many potential advantages including safety. Light therapy has been suggested to be beneficial in certain medical conditions such as depression, but this approach remains explored modulation of pain. We investigated the effects light-emitting diodes (LEDs), visible spectrum, on acute sensory thresholds naive rats well experimental neuropathic Rats receiving...
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....
Microglial activation following central nervous system damage or disease often culminates in a respiratory burst that is necessary for antimicrobial function, but, paradoxically, can bystander cells. We show several K + channels are expressed and play role the of cultured rat microglia. Three pharmacologically separable currents had properties Kv1.3 Ca 2+ /calmodulin-gated channels, SK2, SK3, SK4. mRNA was detected Kv1.3, Kv1.5, and/or Protein SK3 (selective SK2 SK4 antibodies not...
Abstract Background High-mobility group box-1 protein (HMGB1) is a nuclear that regulates gene expression throughout the body. It can also become cytoplasmic and function as neuromodulatory cytokine after tissue damage or injury. The manner in which HMGB1 influences peripheral nervous system following nerve injury unclear. present study investigated degree to signaling contributes maintenance of neuropathic pain behavior rodent. Results Redistribution from nucleus cytoplasm occurred both...
CRMP2, also known as DPYSL2/DRP2, Unc-33, Ulip or TUC2, is a cytosolic phosphoprotein that mediates axon/dendrite specification and axonal growth. Mapping the CRMP2 interactome has revealed previously unappreciated functions subserved by this protein. Together with its canonical roles in neurite growth retraction kinesin-dependent transport, it now interacts numerous binding partners to affect microtubule dynamics; protein endocytosis vesicular cycling, synaptic assembly, calcium channel...
In Brief Targeting proteins within the N-type voltage-gated calcium channel (CaV2.2) complex has proven to be an effective strategy for developing novel pain therapeutics. We describe a peptide aptamer derived from collapsin response mediator protein 2 (CRMP2), CaV2.2-regulatory protein. Addition of 14-carbon myristate group (myr-tat-CBD3) tethered it membrane primary sensory neurons near surface CaV2.2. Pull-down studies demonstrated that myr-tat-CBD3 interfered with CRMP2–CaV2.2...
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. Patients with NF1 commonly experience severe pain. Studies on mice haploinsufficiency have been instructive in identifying sensitization ion channels as possible cause underlying heightened pain suffered by patients NF1. However, behavioral assessments led uncertain conclusions about potential causal role We used clustered regularly interspaced short palindromic repeats...
Collapsin response mediator protein 2 (CRMP2) is traditionally viewed as an axonal growth involved in axon/dendrite specification. Here, we describe novel functions of CRMP2. A 15-amino acid peptide from CRMP2, fused to the TAT cell-penetrating motif HIV-1 protein, TAT-CBD3, but not CBD3 without TAT, attenuated N-methyl-d-aspartate receptor (NMDAR) activity and protected neurons against glutamate-induced Ca(2+) dysregulation, suggesting key contribution CRMP2 these processes. In addition, or...
Pain is more prevalent in women for reasons that remain unclear. We have identified a mechanism of injury-free nociceptor sensitization and opioid-induced hyperalgesia (OIH) promoted by prolactin (PRL) females. PRL signals through mutually inhibitory long (PRLR-L) short (PRLR-S) receptor isoforms, PRLR-S activation induces neuronal excitability. PRLR expression were higher CRISPR-mediated editing PRLR-L allodynia naïve, uninjured female mice depended on circulating PRL. Opioids, but not...
RNA dysregulation likely contributes to disease pathogenesis of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. A pathological form the transactive response (TAR) DNA binding protein (TDP-43) binds in stress granules forms membraneless, amyloid-like TDP-43 aggregates cytoplasm ALS motor neurons. In this study, we hypothesized that by targeting recognition motif (RRM) domains confer a pathogenic interaction between RNA, neuron toxicity could be reduced. silico...