Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Physalin F via Block of CaV2.3 (R-Type) and CaV2.2 (N-Type) Voltage-Gated Calcium Channels.

Abstract:

:No universally efficacious therapy exists for chronic pain, a disease affecting one-fifth of the global population. An overreliance on the prescription of opioids for chronic pain despite their poor ability to improve function has led to a national opioid crisis. In 2018, the NIH launched a Helping to End Addiction Long-term plan to spur discovery and validation of novel targets and mechanisms to develop alternative nonaddictive treatment options. Phytochemicals with medicinal properties have long been used for various treatments worldwide. The natural product physalin F, isolated from the Physalis acutifolia (family: Solanaceae) herb, demonstrated antinociceptive effects in models of inflammatory pain, consistent with earlier reports of its anti-inflammatory and immunomodulatory activities. However, the target of action of physalin F remained unknown. Here, using whole-cell and slice electrophysiology, competition binding assays, and experimental models of neuropathic pain, we uncovered a molecular target for physalin F's antinociceptive actions. We found that physalin F (i) blocks CaV2.3 (R-type) and CaV2.2 (N-type) voltage-gated calcium channels in dorsal root ganglion (DRG) neurons, (ii) does not affect CaV3 (T-type) voltage-gated calcium channels or voltage-gated sodium or potassium channels, (iii) does not bind G-protein coupled opioid receptors, (iv) inhibits the frequency of spontaneous excitatory postsynaptic currents (EPSCs) in spinal cord slices, and (v) reverses tactile hypersensitivity in models of paclitaxel-induced peripheral neuropathy and spinal nerve ligation. Identifying CaV2.2 as a molecular target of physalin F may spur its use as a tool for mechanistic studies and position it as a structural template for future synthetic compounds.

journal_name

ACS Chem Neurosci

authors

Shan Z,Cai S,Yu J,Zhang Z,Vallecillo TGM,Serafini MJ,Thomas AM,Pham NYN,Bellampalli SS,Moutal A,Zhou Y,Xu GB,Xu YM,Luo S,Patek M,Streicher JM,Gunatilaka AAL,Khanna R

doi

10.1021/acschemneuro.9b00166

subject

Has Abstract

pub_date

2019-06-19 00:00:00

pages

2939-2955

issue

6

issn

1948-7193

journal_volume

10

pub_type

杂志文章
  • CuATSM Protects Against the In Vitro Cytotoxicity of Wild-Type-Like Copper-Zinc Superoxide Dismutase Mutants but not Mutants That Disrupt Metal Binding.

    abstract::Mutations in the SOD1 gene are associated with some forms of familial amyotrophic lateral sclerosis (fALS). There are more than 150 different mutations in the SOD1 gene that have various effects on the copper-zinc superoxide dismutase (SOD1) enzyme structure, including the loss of metal binding and a decrease in dimer...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00527

    authors: Farrawell NE,Yerbury MR,Plotkin SS,McAlary L,Yerbury JJ

    更新日期:2019-03-20 00:00:00

  • Classics in Chemical Neuroscience: Haloperidol.

    abstract::The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.7b00018

    authors: Tyler MW,Zaldivar-Diez J,Haggarty SJ

    更新日期:2017-03-15 00:00:00

  • Exosomes in Parkinson's Disease: Current Perspectives and Future Challenges.

    abstract::Exosomes, which are lipid bilayer membrane vesicles, have been implicated as carriers of biological macromolecules. In recent years, the functions of exosomes in the spreading of pathological conversion of proteins among neurons have drawn particular attention in Parkinson's disease research. Extracellular α-synuclein...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00469

    authors: Yuan L,Li JY

    更新日期:2019-02-20 00:00:00

  • Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry.

    abstract::Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.6b00120

    authors: Roux A,Jackson SN,Muller L,Barbacci D,O'Rourke J,Thanos PK,Volkow ND,Balaban C,Schultz JA,Woods AS

    更新日期:2016-08-17 00:00:00

  • Impact on Glioblastoma U87 Cell Gene Expression of a Carborane Cluster-Bearing Amino Acid: Implications for Carborane Toxicity in Mammalian Cells.

    abstract::Carboranes have been extensively investigated as potential drugs for the treatment of malignant human brain tumors by boron neutron capture therapy (BNCT). This noninvasive treatment modality utilizes compounds containing the nonradioactive isotope 10B which has a high propensity to capture slow neutrons. In response,...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00512

    authors: He T,Chittur SV,Musah RA

    更新日期:2019-03-20 00:00:00

  • Analysis and synthesis in olfaction.

    abstract::Natural environments contain numerous volatile compounds emanating from a large number of sources, and the survival of many animals depends on their ability to segregate odors of interest within complex odorous scenes. In a recent paper, we described how the ability of mice to detect odors within mixtures depends on t...

    journal_title:ACS chemical neuroscience

    pub_type: 评论,杂志文章

    doi:10.1021/cn500199n

    authors: Rokni D,Murthy VN

    更新日期:2014-10-15 00:00:00

  • A new method to image heme-Fe, total Fe, and aggregated protein levels after intracerebral hemorrhage.

    abstract::An intracerebral hemorrhage (ICH) is a devastating stroke that results in high mortality and significant disability in survivors. Unfortunately, the underlying mechanisms of this injury are not yet fully understood. After the primary (mechanical) trauma, secondary degenerative events contribute to ongoing cell death i...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00037

    authors: Hackett MJ,DeSouza M,Caine S,Bewer B,Nichol H,Paterson PG,Colbourne F

    更新日期:2015-05-20 00:00:00

  • Rethinking Glioblastoma Therapy: MDA-9/Syntenin Targeted Small Molecule.

    abstract::Effective therapies for glioblastoma multiforme (GBM) are not currently available. A small molecule has been identified using fragment-based drug-discovery guided by NMR that targets important protein-protein interactions controlling GBM invasion and pathogenicity. This first generation drug displays excellent pharmac...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.9b00016

    authors: Das SK,Sarkar D,Cavenee WK,Emdad L,Fisher PB

    更新日期:2019-03-20 00:00:00

  • DARK Classics in Chemical Neuroscience: Krokodil.

    abstract::Krokodil is the street name for a homemade mixture that has been used as a cheap substitute for heroin. The main active substance in krokodil is desomorphine, an opioid that is 10 times more potent than morphine. Krokodil use began in Russia and Ukraine but has spread throughout several countries in Europe and North A...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00495

    authors: Alves EA

    更新日期:2020-09-17 00:00:00

  • Effects of Zn2+ binding on the structural and dynamic properties of amyloid β peptide associated with Alzheimer's disease: Asp1 or Glu11?

    abstract::Extensive experimental and computational studies have suggested that multiple Zn(2+) binding modes in amyloid β (Aβ) peptides could exist simultaneously. However, consistent results have not been obtained for the effects of Zn(2+) binding on Aβ structure, dynamics, and kinetics in particular. Some key questions such a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn4001445

    authors: Xu L,Wang X,Wang X

    更新日期:2013-11-20 00:00:00

  • Flavonoids as therapeutic compounds targeting key proteins involved in Alzheimer's disease.

    abstract::Alzheimer's disease is characterized by pathological aggregation of protein tau and amyloid-β peptides, both of which are considered to be toxic to neurons. Naturally occurring dietary flavonoids have received considerable attention as alternative candidates for Alzheimer's therapy taking into account their antiamyloi...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn400213r

    authors: Baptista FI,Henriques AG,Silva AM,Wiltfang J,da Cruz e Silva OA

    更新日期:2014-02-19 00:00:00

  • Imaging chemical neurotransmission with genetically encoded fluorescent sensors.

    abstract::A major challenge in neuroscience is to decipher the logic of neural circuitry and to link it to learning, memory, and behavior. Synaptic transmission is a critical event underlying information processing within neural circuitry. In the extracellular space, the concentrations and distributions of excitatory, inhibitor...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn500280k

    authors: Liang R,Broussard GJ,Tian L

    更新日期:2015-01-21 00:00:00

  • Development of a new photochromic ion channel blocker via azologization of fomocaine.

    abstract::Photochromic blockers of voltage gated ion channels are powerful tools for the control of neuronal systems with high spatial and temporal precision. We now introduce fotocaine, a new type of photochromic channel blocker based on the long-lasting anesthetic fomocaine. Fotocaine is readily taken up by neurons in brain s...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn500070w

    authors: Schoenberger M,Damijonaitis A,Zhang Z,Nagel D,Trauner D

    更新日期:2014-07-16 00:00:00

  • Autoimmune Attack of the Neuromuscular Junction in Myasthenia Gravis: Nicotinic Acetylcholine Receptors and Other Targets.

    abstract::The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system,...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.9b00041

    authors: Paz ML,Barrantes FJ

    更新日期:2019-05-15 00:00:00

  • Serotonin: A New Hope in Alzheimer's Disease?

    abstract::Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enha...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00135

    authors: Claeysen S,Bockaert J,Giannoni P

    更新日期:2015-07-15 00:00:00

  • Activation of Dopamine D3 Receptor Subtypes Inhibits the Neurogenic Systemic Vasodilation Induced by Stimulation of the Perivascular CGRPergic Discharge.

    abstract::The sensory nervous system controls cardiovascular homeostasis via capsaicin-sensitive neurons that release calcitonin gene-related peptide (CGRP), which subsequently activates CGRP receptors. How this perivascular CGRPergic discharge is modulated, nevertheless, remains unclear. In pithed rats, systemic vasodilation i...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00277

    authors: Manrique-Maldonado G,Altamirano-Espinoza AH,Rivera-Mancilla E,Hernández-Abreu O,Villalón CM

    更新日期:2019-08-21 00:00:00

  • Neuromicrobiology: How Microbes Influence the Brain.

    abstract::We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in h...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.7b00373

    authors: de la Fuente-Nunez C,Meneguetti BT,Franco OL,Lu TK

    更新日期:2018-02-21 00:00:00

  • Phospho-Tau Impairs Nuclear-Cytoplasmic Transport.

    abstract::Aggregation of hyperphosphorylated tau is the hallmark of several tauopathies, including Alzheimer's disease (AD). Although the mechanism underlying tau-associated neuronal damage remains unclear, it is believed that tau hyperphosphorylation is one of the key features in disease progression. A recent study demonstrate...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00632

    authors: Tripathi T,Prakash J,Shav-Tal Y

    更新日期:2019-01-16 00:00:00

  • Detection of orexin A neuropeptide in biological fluids using a zinc oxide field effect transistor.

    abstract::Biomarkers which are indicative of acute physiological and emotional states are studied in a number of different areas in cognitive neuroscience. Currently, many cognitive studies are conducted based on programmed tasks followed by timed biofluid sampling, central laboratory processing, and followed by data analysis. ...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn300159e

    authors: Hagen J,Lyon W,Chushak Y,Tomczak M,Naik R,Stone M,Kelley-Loughnane N

    更新日期:2013-03-20 00:00:00

  • Structure of the Brain N-Acetylaspartate Biosynthetic Enzyme NAT8L Revealed by Computer Modeling.

    abstract::We report the results of computational modeling of a three-dimensional all-atom structure of the membrane-associated protein encoded by the NAT8L gene, aspartate N-acetyltransferase, which is essential for brain synthesis of N-acetyl-l-aspartate (NAA). The lack of experimentally derived three-dimensional structures of...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00250

    authors: Polyakov IV,Kniga AE,Grigorenko BL,Nemukhin AV

    更新日期:2020-08-05 00:00:00

  • Preference for Glucose over Inositol Headgroup during Lysolipid Activation of G Protein-Coupled Receptor 55.

    abstract::G protein-coupled receptor 55 (GPR55) is highly expressed in brain and peripheral nervous system. Originally deorphanized as a cannabinoid receptor, recently GPR55 has been described as a lysophospholipid-responsive receptor, specifically toward lysophosphatidylinositol and lysophosphatidyl-β-d-glucoside (LysoPtdGlc)....

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.8b00505

    authors: Guy AT,Kano K,Ohyama J,Kamiguchi H,Hirabayashi Y,Ito Y,Matsuo I,Greimel P

    更新日期:2019-01-16 00:00:00

  • Genetically encoded tools: bridging the gap between neuronal identity and function.

    abstract::Genetically encoded tools are positioned to serve a unique and critical role in bridging the gap between the genetic identity of neurons and their functional properties. However, the use of these tools is limited by our current understanding of cell-type identity. As we make technological advances that focus on captur...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.5b00008

    authors: Cho YK

    更新日期:2015-01-21 00:00:00

  • Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains.

    abstract::Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diag...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00093

    authors: Neo Shin N,Jeon H,Jung Y,Baek S,Lee S,Yoo HC,Bae GH,Park K,Yang SH,Han JM,Kim I,Kim Y

    更新日期:2019-06-19 00:00:00

  • Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget Directed Ligand Approach.

    abstract::No selective drugs exist, and we have been designing, synthesizing, and evaluating multitarget-directed ligands since the beginning of modern medicinal chemistry, without knowing it, most possibly. The challenge to discover the efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD) therapy implies...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/acschemneuro.8b00069

    authors: Oset-Gasque MJ,Marco-Contelles J

    更新日期:2018-03-21 00:00:00

  • Structure-selective anisotropy assay for amyloid Beta oligomers.

    abstract::Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimer's disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebr...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/cn3001262

    authors: Matveeva EG,Rudolph A,Moll JR,Thompson RB

    更新日期:2012-11-21 00:00:00

  • Recent progress on the identification of metabotropic glutamate 4 receptor ligands and their potential utility as CNS therapeutics.

    abstract::This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of th...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章,评审

    doi:10.1021/cn200043e

    authors: Robichaud AJ,Engers DW,Lindsley CW,Hopkins CR

    更新日期:2011-08-17 00:00:00

  • Irrigation System and COVID-19 Recurrence: A Potential Risk Factor in the Transmission of SARS-CoV-2.

    abstract::Several lines of evidence suggest the presence of severe acute respiratory coronavirus-2 (SARS-CoV-2) in wastewater. The use of sewage water for irrigation is common in many developing countries, and it is only partially treated in the majority of countries with less than 10% of collected wastewater receiving any form...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00570

    authors: Siddiqui R,Khamis M,Ibrahim T,Khan NA

    更新日期:2020-10-07 00:00:00

  • Development of Clickable Photoaffinity Ligands for Metabotropic Glutamate Receptor 2 Based on Two Positive Allosteric Modulator Chemotypes.

    abstract::The metabotropic glutamate receptor 2 (mGlu2) is a transmembrane-spanning class C G protein-coupled receptor that is an attractive therapeutic target for multiple psychiatric and neurological disorders. A key challenge has been deciphering the contribution of mGlu2 relative to other closely related mGlu receptors in m...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.0c00009

    authors: Hellyer SD,Aggarwal S,Chen ANY,Leach K,Lapinsky DJ,Gregory KJ

    更新日期:2020-06-03 00:00:00

  • Design and Synthesis of 2,3- trans-Proline Analogues as Ligands for Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters.

    abstract::Development of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00205

    authors: Poulie CBM,Alcaide A,Krell-Jørgensen M,Larsen Y,Astier E,Bjørn-Yoshimoto WE,Yi F,Syrenne JT,Storgaard M,Nielsen B,Frydenvang KA,Jensen AA,Hansen KB,Pickering DS,Bunch L

    更新日期:2019-06-19 00:00:00

  • Neurotensin Analogues Containing Cyclic Surrogates of Tyrosine at Position 11 Improve NTS2 Selectivity Leading to Analgesia without Hypotension and Hypothermia.

    abstract::Neurotensin (NT) exerts its analgesic effects through activation of the G protein-coupled receptors NTS1 and NTS2. This opioid-independent antinociception represents a potential alternative for pain management. While activation of NTS1 also induces a drop in blood pressure and body temperature, NTS2 appears to be an a...

    journal_title:ACS chemical neuroscience

    pub_type: 杂志文章

    doi:10.1021/acschemneuro.9b00390

    authors: Eiselt E,Gonzalez S,Martin C,Chartier M,Betti C,Longpré JM,Cavelier F,Tourwé D,Gendron L,Ballet S,Sarret P

    更新日期:2019-11-20 00:00:00