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Crmp2 AND pain

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https://www.readbyqxmd.com/read/27917413/efficacy-of-s-lacosamide-in-preclinical-models-of-cephalic-pain
#1
Aubin Moutal, Nathan Eyde, Edwin Telemi, Ki Duk Park, Jennifer Y Xie, David W Dodick, Frank Porreca, Rajesh Khanna
Migraine is one of the world's most common neurological disorders. Current acute migraine treatments have sub-optimal efficacy and new therapeutic options are needed. Approaches targeting calcitonin gene related peptide (CGRP) signaling are clinically effective but small molecule antagonists have not been advanced due to toxicity. In this study, we explored the axonal growth/specification collapsin response mediator protein 2 (CRMP2) as a novel "druggable" target for inhibiting CGRP release and for potential relevance for treatment of migraine pain...
June 2016: Pain Reports (Baltimore, Md.)
https://www.readbyqxmd.com/read/27537210/sustained-relief-of-ongoing-experimental-neuropathic-pain-by-a-crmp2-peptide-aptamer-with-low-abuse-potential
#2
Jennifer Y Xie, Lindsey A Chew, Xiaofang Yang, Yuying Wang, Chaoling Qu, Yue Wang, Lauren M Federici, Stephanie D Fitz, Matthew S Ripsch, Michael R Due, Aubin Moutal, May Khanna, Fletcher A White, Todd W Vanderah, Philip L Johnson, Frank Porreca, Rajesh Khanna
Uncoupling the protein-protein interaction between collapsin response mediator protein 2 (CRMP2) and N-type voltage-gated calcium channel (CaV2.2) with an allosteric CRMP2-derived peptide (CBD3) is antinociceptive in rodent models of inflammatory and neuropathic pain. We investigated the efficacy, duration of action, abuse potential, and neurobehavioral toxicity of an improved mutant CRMP2 peptide. A homopolyarginine (R9)-conjugated CBD3-A6K (R9-CBD3-A6K) peptide inhibited the CaV2.2-CRMP2 interaction in a concentration-dependent fashion and diminished surface expression of CaV2...
September 2016: Pain
https://www.readbyqxmd.com/read/26967696/-s-lacosamide-inhibition-of-crmp2-phosphorylation-reduces-postoperative-and-neuropathic-pain-behaviors-through-distinct-classes-of-sensory-neurons-identified-by-constellation-pharmacology
#3
Aubin Moutal, Lindsey A Chew, Xiaofang Yang, Yue Wang, Seul Ki Yeon, Edwin Telemi, Seeneen Meroueh, Ki Duk Park, Raghuraman Shrinivasan, Kerry B Gilbraith, Chaoling Qu, Jennifer Y Xie, Amol Patwardhan, Todd W Vanderah, May Khanna, Frank Porreca, Rajesh Khanna
Chronic pain affects the life of millions of people. Current treatments have deleterious side effects. We have advanced a strategy for targeting protein interactions which regulate the N-type voltage-gated calcium (CaV2.2) channel as an alternative to direct channel block. Peptides uncoupling CaV2.2 interactions with the axonal collapsin response mediator protein 2 (CRMP2) were antinociceptive without effects on memory, depression, and reward/addiction. A search for small molecules that could recapitulate uncoupling of the CaV2...
July 2016: Pain
https://www.readbyqxmd.com/read/26944284/a-tale-of-the-good-and-bad-remodeling-of-the-microtubule-network-in-the-brain-by-cdk5
#4
Kavita Shah, Debomoy K Lahiri
Cdk5, a cyclin-dependent kinase family member, is a global orchestrator of neuronal cytoskeletal dynamics. During embryogenesis, Cdk5 is indispensable for brain development. In adults, it is essential for numerous neuronal processes, including higher cognitive functions such as learning and memory formation, drug addiction, pain signaling, and long-term behavior changes through long-term potentiation and long-term depression, all of which rely on rapid alterations in the cytoskeleton. Cdk5 activity becomes deregulated in various brain disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, attention-deficit hyperactivity disorder, epilepsy, schizophrenia, and ischemic stroke; these all result in profound remodeling of the neuronal cytoskeleton...
March 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/26077693/crmps-critical-molecules-for-neurite-morphogenesis-and-neuropsychiatric-diseases
#5
REVIEW
T T Quach, J Honnorat, P E Kolattukudy, R Khanna, A M Duchemin
Neuronal polarity and spatial rearrangement of neuronal processes are central to the development of all mature nervous systems. Recent studies have highlighted the dynamic expression of Collapsin-Response-Mediator Proteins (CRMPs) in neuronal dendritic/axonal compartments, described their interaction with cytoskeleton proteins, identified their ability to activate L- and N-type voltage-gated calcium channels (VGCCs) and delineated their crucial role as signaling molecules essential for neuron differentiation and neural network development and maintenance...
September 2015: Molecular Psychiatry
https://www.readbyqxmd.com/read/25921334/the-protein-interactome-of-collapsin-response-mediator-protein-2-crmp2-dpysl2-reveals-novel-partner-proteins-in-brain-tissue
#6
REVIEW
Daniel Martins-de-Souza, Juliana S Cassoli, Juliana M Nascimento, Kenneth Hensley, Paul C Guest, Andres M Pinzon-Velasco, Christoph W Turck
PURPOSE: Collapsin response mediator protein-2 (CRMP2) is a CNS protein involved in neuronal development, axonal and neuronal growth, cell migration, and protein trafficking. Recent studies have linked perturbations in CRMP2 function to neurodegenerative disorders such as Alzheimer's disease, neuropathic pain, and Batten disease, and to psychiatric disorders such as schizophrenia. Like most proteins, CRMP2 functions though interactions with a molecular network of proteins and other molecules...
October 2015: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/25782368/a-membrane-delimited-n-myristoylated-crmp2-peptide-aptamer-inhibits-cav2-2-trafficking-and-reverses-inflammatory-and-postoperative-pain-behaviors
#7
Liberty Fran├žois-Moutal, Yue Wang, Aubin Moutal, Karissa E Cottier, Ohannes K Melemedjian, Xiaofang Yang, Yuying Wang, Weina Ju, Tally M Largent-Milnes, May Khanna, Todd W Vanderah, Rajesh Khanna
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 novel peptide aptamer derived from the collapsin response mediator protein 2 (CRMP2), a CaV2.2-regulatory protein. Addition of a 14-carbon myristate group to the peptide (myr-tat-CBD3) tethered it to the membrane of primary sensory neurons near surface CaV2.2. Pull-down studies demonstrated that myr-tat-CBD3 peptide interfered with the CRMP2-CaV2...
July 2015: Pain
https://www.readbyqxmd.com/read/23831344/challenging-the-catechism-of-therapeutics-for-chronic-neuropathic-pain-targeting-cav2-2-interactions-with-crmp2-peptides
#8
REVIEW
Polina Feldman, Rajesh Khanna
Chronic neuropathic pain management is a worldwide concern. Pharmaceutical companies globally have historically targeted ion channels as the therapeutic catechism with many blockbuster successes. Remarkably, no new pain therapeutic has been approved by European or American regulatory agencies over the last decade. This article will provide an overview of an alternative approach to ion channel drug discovery: targeting regulators of ion channels, specifically focusing on voltage-gated calcium channels. We will highlight the discovery of an anti-nociceptive peptide derived from a novel calcium channel interacting partner - the collapsin response mediator protein 2 (CRMP2)...
December 17, 2013: Neuroscience Letters
https://www.readbyqxmd.com/read/23106100/suppression-of-pain-related-behavior-in-two-distinct-rodent-models-of-peripheral-neuropathy-by-a-homopolyarginine-conjugated-crmp2-peptide
#9
Weina Ju, Qi Li, Yohance M Allette, Matthew S Ripsch, Fletcher A White, Rajesh Khanna
The N-type voltage-gated calcium channel (CaV2.2) is a clinically endorsed target in chronic pain treatments. As directly targeting the channel can lead to multiple adverse side effects, targeting modulators of CaV2.2 may prove better. We previously identified ST1-104, a short peptide from the collapsin response mediator protein 2 (CRMP2), which disrupted the CaV2.2-CRMP2 interaction and suppressed a model of HIV-related neuropathy induced by anti-retroviral therapy but not traumatic neuropathy. Here, we report ST2-104 -a peptide wherein the cell-penetrating TAT motif has been supplanted with a homopolyarginine motif, which dose-dependently inhibits the CaV2...
March 2013: Journal of Neurochemistry
https://www.readbyqxmd.com/read/22891239/inhibition-of-transmitter-release-and-attenuation-of-anti-retroviral-associated-and-tibial-nerve-injury-related-painful-peripheral-neuropathy-by-novel-synthetic-ca2-channel-peptides
#10
Sarah M Wilson, Brian S Schmutzler, Joel M Brittain, Erik T Dustrude, Matthew S Ripsch, Jessica J Pellman, Tae-Sung Yeum, Joyce H Hurley, Cynthia M Hingtgen, Fletcher A White, Rajesh Khanna
N-type Ca(2+) channels (CaV2.2) are a nidus for neurotransmitter release and nociceptive transmission. However, the use of CaV2.2 blockers in pain therapeutics is limited by side effects resulting from inhibition of the physiological functions of CaV2.2 within the CNS. We identified an anti-nociceptive peptide (Brittain, J. M., Duarte, D. B., Wilson, S. M., Zhu, W., Ballard, C., Johnson, P. L., Liu, N., Xiong, W., Ripsch, M. S., Wang, Y., Fehrenbacher, J. C., Fitz, S. D., Khanna, M., Park, C. K., Schmutzler, B...
October 12, 2012: Journal of Biological Chemistry
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