当前位置： SCI文献检索 > ACS Chemical Neuroscience期刊下所有文献 > Identifying New AMP-Activated Protein Kinase Inhibitors That Protect against Ischemic Brain Injury.

Identifying New AMP-Activated Protein Kinase Inhibitors That Protect against Ischemic Brain Injury.

Abstract：

:We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc neurotoxicity representing at least one mechanism of ischemic neuronal death. Inhibition of AMPK could be a viable therapeutic strategy to prevent ischemic brain injury following stroke. This prompted our search for novel inhibitors of AMPK activity and zinc-induced neuronal death using cultured mouse cortex and a rat model of brain injury after middle cerebral artery occlusion (MCAO). In structure-based virtual screening, 118 compounds were predicted to bind the active site of AMPK α2, and 40 showed in vitro AMPK α2 inhibitory activity comparable to compound C (a well-known, potent AMPK inhibitor). In mouse cortical neuronal cultures, 7 of 40 compound reduced zinc-induced neuronal death at levels comparable to compound C. Ultimately, only agents 2G11 and 1H10 significantly attenuated various types of neuronal death, including oxidative stress, excitotoxicity, and apoptosis. When administered as intracerebroventricular injections prior to permanent MCAO in rats, 2G11 and 1H10 reduced brain infarct volumes, whereas compound C did not. Therefore, these novel AMPK inhibitors could be drug development candidates to treat stroke.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

Eom JW,Kim TY,Seo BR,Park H,Koh JY,Kim YH

doi

10.1021/acschemneuro.8b00654

subject

Has Abstract

pub_date

2019-05-15 00:00:00

pages

2345-2354

issue

5

issn

1948-7193

journal_volume

10

pub_type

杂志文章

相关文献

ACS Chemical Neuroscience文献大全
  • Hydroxylated Single-Walled Carbon Nanotubes Inhibit Aβ42 Fibrillogenesis, Disaggregate Mature Fibrils, and Protect against Aβ42-Induced Cytotoxicity.

    abstract：:The fibrillogenesis of amyloid-β protein (Aβ) is considered a crucial factor in the pathogenesis of Alzheimer's disease (AD). Hence, inhibiting Aβ fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against Aβ fibrillo...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.8b00441

    authors： Liu F,Wang W,Sang J,Jia L,Lu F

    更新日期：2019-01-16 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

  • Water-soluble mmp-9 inhibitor prodrug generates active metabolites that cross the blood-brain barrier.

    abstract：:MMP-9 plays a detrimental role in the pathology of several neurological diseases and, thus, represents an important target for intervention. The water-soluble prodrug ND-478 is hydrolyzed to the active MMP-9 inhibitor ND-322, which in turn is N-acetylated to the even more potent metabolite ND-364. We used a sensitive ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn400077d

    authors： Song W,Peng Z,Gooyit M,Suckow MA,Schroeder VA,Wolter WR,Lee M,Ikejiri M,Cui J,Gu Z,Chang M

    更新日期：2013-08-21 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

  • Neurons and tumor suppressors.

    abstract：:Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/cn500110p

    authors： Zochodne DW

    更新日期：2014-08-20 00:00:00

  • Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    abstract：:High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosin...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn500001m

    authors： Morales-Figueroa GE,Márquez-Gómez R,González-Pantoja R,Escamilla-Sánchez J,Arias-Montaño JA

    更新日期：2014-08-20 00:00:00

  • D-serine uptake and release in PC-12 cells measured by chiral microchip electrophoresis-mass spectrometry.

    abstract：:Previous work has established that D-serine (D-Ser) plays important roles in certain neurological processes. Study on its uptake/storage and release by neuronal cells is highly significant for elucidating relevant mechanisms. In this work, PC-12 cells were incubated with racemic Ser (100 μM each enantiomer). After inc...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn5003122

    authors： Li X,McCullum C,Zhao S,Hu H,Liu YM

    更新日期：2015-04-15 00:00:00

  • Targeting Chondroitin Sulfate Proteoglycans: An Emerging Therapeutic Strategy to Treat CNS Injury.

    abstract：:Chondroitin sulfate proteoglycans (CSPGs) are the most abundant components of glial scar formed after severe traumatic brain injury as well as spinal cord injury and play a crucial inhibitory role in axonal regeneration by selective contraction of filopodia of the growth cone of sprouting neurites. Healing of central ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.0c00004

    authors： Mukherjee N,Nandi S,Garg S,Ghosh S,Ghosh S,Samat R,Ghosh S

    更新日期：2020-02-05 00:00:00

  • Structural Modeling of γ-Secretase Aβ n Complex Formation and Substrate Processing.

    abstract：:The intramembrane aspartyl protease γ-secretase (GSEC) cleaves single-span transmembrane helices including the C-terminal fragment of the amyloid precursor protein (APP). This substrate is initially cleaved at the ϵ-site followed by successive processing (trimming) events mostly in steps of three amino acids. GSEC is ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.8b00725

    authors： Hitzenberger M,Zacharias M

    更新日期：2019-03-20 00:00:00

  • Ethylatropine Bromide as a Peripherally Restricted Muscarinic Antagonist.

    abstract：:Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent o...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.6b00334

    authors： Rojas A,Ganesh T,Walker A,Dingledine R

    更新日期：2017-04-19 00:00:00

  • Investigation of a calcium-responsive contrast agent in cellular model systems: feasibility for use as a smart molecular probe in functional MRI.

    abstract：:Responsive or smart contrast agents (SCAs) represent a promising direction for development of novel functional MRI (fMRI) methods for the eventual noninvasive assessment of brain function. In particular, SCAs that respond to Ca(2+) may allow tracking neuronal activity independent of brain vasculature, thus avoiding th...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn500049n

    authors： Angelovski G,Gottschalk S,Milošević M,Engelmann J,Hagberg GE,Kadjane P,Andjus P,Logothetis NK

    更新日期：2014-05-21 00:00:00

  • d-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study.

    abstract：:The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in t...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.6b00398

    authors： Weatherly CA,Du S,Parpia C,Santos PT,Hartman AL,Armstrong DW

    更新日期：2017-06-21 00:00:00

  • Pharmacological Characterizations of anti-Dementia Memantine Nitrate via Neuroprotection and Vasodilation in Vitro and in Vivo.

    abstract：:We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00242

    authors： Mak S,Liu Z,Wu L,Guo B,Luo F,Liu Z,Hu S,Wang J,Cui G,Sun Y,Wang Y,Zhang G,Han Y,Zhang Z

    更新日期：2020-02-05 00:00:00

  • Luciferins behave like drugs.

    abstract：:The light emission chemistry of firefly luciferase can be harnessed to reveal otherwise invisible biological processes occurring in the brains of live animals. Though powerful, the need for the luciferase substrate D-luciferin to traverse the blood-brain barrier poses limitations on the sensitivity and interpretation ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.5b00195

    authors： Mofford DM,Miller SC

    更新日期：2015-08-19 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

  • Molecular Dynamics Study on the Inhibition Mechanisms of Drugs CQ1-3 for Alzheimer Amyloid-β40 Aggregation Induced by Cu(2.).

    abstract：:The aggregation of amyloid-β (Aβ) peptide induced by Cu(2+) is a key factor in development of Alzheimer's disease (AD), and metal ion chelation therapy enables treatment of AD. Three CQi (i = 1, 2, and 3 with R = H, Cl, and NO2, respectively) drugs had been verified experimentally to be much stronger inhibitors than t...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.5b00343

    authors： Dong M,Li H,Hu D,Zhao W,Zhu X,Ai H

    更新日期：2016-05-18 00:00:00

  • Probing the neurochemical correlates of motivation and decision making.

    abstract：:Online electrochemical detection techniques are the state-of-the-art for evaluating chemical communication in the brain underlying motivated behavior and decision making. In this Viewpoint, we discuss avenues for future technological development, as well as the requirement for increasingly sophisticated and interdisci...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/cn500322y

    authors： Wassum KM,Phillips PE

    更新日期：2015-01-21 00:00:00

  • Simultaneous determination of all forms of biopterin and neopterin in cerebrospinal fluid.

    abstract：:In humans, genetic defects of the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor in hydroxylation reactions, are associated with severe neurological disorders. The diagnosis of these conditions relies on the determination of BH4, dihydrobiopterin (BH2), and dihydroneopterin (NH2) in cere...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn4001928

    authors： Guibal P,Lévêque N,Doummar D,Giraud N,Roze E,Rodriguez D,Couderc R,Billette De Villemeur T,Moussa F

    更新日期：2014-07-16 00:00:00

  • Correlation between Cellular Uptake and Cytotoxicity of Fragmented α-Synuclein Amyloid Fibrils Suggests Intracellular Basis for Toxicity.

    abstract：:Aggregation and intracellular deposition of the protein α-synuclein is an underlying characteristic of Parkinson's disease. α-Synuclein assemblies also undergo cell-cell spreading, facilitating propagation of their cellular pathology. Understanding how cellular interactions and uptake of extracellular α-synuclein asse...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00562

    authors： Zhang X,Wesén E,Kumar R,Bernson D,Gallud A,Paul A,Wittung-Stafshede P,Esbjörner EK

    更新日期：2020-02-05 00:00:00

  • A Novel Negative Allosteric Modulator Selective for GluN2C/2D-Containing NMDA Receptors Inhibits Synaptic Transmission in Hippocampal Interneurons.

    abstract：:N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties a...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.7b00329

    authors： Swanger SA,Vance KM,Acker TM,Zimmerman SS,DiRaddo JO,Myers SJ,Bundgaard C,Mosley CA,Summer SL,Menaldino DS,Jensen HS,Liotta DC,Traynelis SF

    更新日期：2018-02-21 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

  • Synaptic plasticity, a symphony in GEF.

    abstract：:Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn100012x

    authors： Kiraly DD,Eipper-Mains JE,Mains RE,Eipper BA

    更新日期：2010-05-19 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

  • Investigation of the Role of Chirality in the Interaction with σ Receptors and Effect on Binge Eating Episode of a Potent σ1 Antagonist Analogue of Spipethiane.

    abstract：:The enantiomers of the potent σ1 receptor antagonist (±)-1 were synthesized and evaluated for their affinity at σ1, σ2 receptors and dopamine transporter (DAT). Analogously to (±)-1, both of the enantiomers showed very high affinity for the σ1 receptor and unprecedented selectivity over both the σ2 receptor and DAT. T...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00261

    authors： Del Bello F,Micioni Di Bonaventura MV,Bonifazi A,Wünsch B,Schepmann D,Giancola JB,Micioni Di Bonaventura E,Vistoli G,Giorgioni G,Quaglia W,Piergentili A,Cifani C

    更新日期：2019-08-21 00:00:00

  • Olive Oil Lignan (+)-Acetoxypinoresinol Peripheral Motor and Neuronal Protection against the Tremorgenic Mycotoxin Penitrem A Toxicity via STAT1 Pathway.

    abstract：:Penitrem A, PA, is an indole diterpene alkaloid produced by several fungal species. PA acts as a selective Ca2+-dependent K-channels (Maxi-K, BK) antagonist in brain, causing motor system dysfunctions including tremors and seizures. However, its molecular mechanism at the peripheral nervous system (PNS) is still ambig...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.0c00458

    authors： Qusa MH,Abdelwahed KS,Meyer SA,El Sayed KA

    更新日期：2020-11-04 00:00:00

  • A novel restricted diffusion model of evoked dopamine.

    abstract：:In vivo fast-scan cyclic voltammetry provides high-fidelity recordings of electrically evoked dopamine release in the rat striatum. The evoked responses are suitable targets for numerical modeling because the frequency and duration of the stimulus are exactly known. Responses recorded in the dorsal and ventral striatu...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/cn5000666

    authors： Walters SH,Taylor IM,Shu Z,Michael AC

    更新日期：2014-09-17 00:00:00

  • Misfolded SOD1 Accumulation and Mitochondrial Association Contribute to the Selective Vulnerability of Motor Neurons in Familial ALS: Correlation to Human Disease.

    abstract：:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.7b00140

    authors： Abu-Hamad S,Kahn J,Leyton-Jaimes MF,Rosenblatt J,Israelson A

    更新日期：2017-10-18 00:00:00

  • Endogenous Serotonin 5-HT2A and 5-HT2C Receptors Associate in the Medial Prefrontal Cortex.

    abstract：:The 5-HT2A receptor (5-HT2AR) and 5-HT2CR are localized to the same neurons within the medial prefrontal cortex (mPFC), which regulates executive function, decision-making, and reward-guided learning and memory processes. The 5-HT2AR and 5-HT2CR coimmunoprecipitate in the mPFC of male Sprague-Dawley rats, while in vit...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.8b00669

    authors： Price AE,Sholler DJ,Stutz SJ,Anastasio NC,Cunningham KA

    更新日期：2019-07-17 00:00:00

  • Synthesis and pharmacology of halogenated δ-opioid-selective [d-Ala(2)]deltorphin II peptide analogues.

    abstract：:Deltorphins are naturally occurring peptides produced by the skin of the giant monkey frog (Phyllomedusa bicolor). They are δ-opioid receptor-selective agonists. Herein, we report the design and synthesis of a peptide, Tyr-d-Ala-(pI)Phe-Glu-Ile-Ile-Gly-NH2 3 (GATE3-8), based on the [d-Ala(2)]deltorphin II template, wh...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.5b00060

    authors： Pescatore R,Marrone GF,Sedberry S,Vinton D,Finkelstein N,Katlowitz YE,Pasternak GW,Wilson KR,Majumdar S

    更新日期：2015-06-17 00:00:00

  • The molecular basis of memory. Part 2: chemistry of the tripartite mechanism.

    abstract：:We propose a tripartite mechanism to describe the processing of cognitive information (cog-info), comprising the (1) neuron, (2) surrounding neural extracellular matrix (nECM), and (3) numerous "trace" metals distributed therein. The neuron is encased in a polyanionic nECM lattice doped with metals (>10), wherein it p...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/cn300237r

    authors： Marx G,Gilon C

    更新日期：2013-06-19 00:00:00