1,963 results match your criteria ACS chemical neuroscience[Journal]


In This Issue, Volume 10, Issue 4.

ACS Chem Neurosci 2019 Apr;10(4):1866

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http://dx.doi.org/10.1021/acschemneuro.9b00193DOI Listing

NeuroChat with Professor Steven Townsend.

Authors:
Craig W Lindsley

ACS Chem Neurosci 2019 Apr;10(4):2082-2083

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http://dx.doi.org/10.1021/acschemneuro.9b00169DOI Listing

Precision Medicine in Epilepsy-The Way Forward?

ACS Chem Neurosci 2019 Apr;10(4):2080-2081

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http://dx.doi.org/10.1021/acschemneuro.9b00162DOI Listing

In This Issue, Volume 9, Issue 2.

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ACS Chem Neurosci 2018 Feb;9(2):140

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http://dx.doi.org/10.1021/acschemneuro.8b00050DOI Listing
February 2018

In This Issue, Volume 10, Issue 1.

ACS Chem Neurosci 2019 Jan;10(1)

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http://dx.doi.org/10.1021/acschemneuro.8b00731DOI Listing
January 2019

In This Issue, Volume 9, Issue 12.

ACS Chem Neurosci 2018 Dec;9(12):2879

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http://dx.doi.org/10.1021/acschemneuro.8b00672DOI Listing
December 2018

In This Issue, Volume 9, Issue 4.

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ACS Chem Neurosci 2018 Apr;9(4):628

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http://dx.doi.org/10.1021/acschemneuro.8b00153DOI Listing

In This Issue, Volume 9, Issue 6.

ACS Chem Neurosci 2018 Jun;9(6):1225

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http://dx.doi.org/10.1021/acschemneuro.8b00275DOI Listing

In This Issue, Volume 9, Issue 3.

ACS Chem Neurosci 2018 Mar;9(3):392

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http://dx.doi.org/10.1021/acschemneuro.8b00108DOI Listing

In This Issue, Volume 9, Issue 5.

ACS Chem Neurosci 2018 May;9(5):869

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http://dx.doi.org/10.1021/acschemneuro.8b00216DOI Listing

The O-GlcNAc modification protects against protein misfolding and aggregation in neurodegenerative disease.

ACS Chem Neurosci 2019 Apr 15. Epub 2019 Apr 15.

Post-translational modifications (PTM) of proteins are becoming the focus of intense research due to their implications in a broad spectrum of neurodegenerative diseases. Various PTMs have been identified to alter the toxic profiles of proteins which play critical roles in disease etiology. In Alzheimer's disease (AD), dysregulated phosphorylation is reported to promote pathogenic processing of the microtubule-associated tau protein. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00143DOI Listing

Electrochemical immunosensor for TNFα-mediated inflammatory disease screening.

ACS Chem Neurosci 2019 Apr 15. Epub 2019 Apr 15.

Inflammation associated to cancer, neurodegenerative, ocular and autoimmune diseases has a considerable impact in public health. Tumor necrosis factor alpha (TNFα) is a key mediator of inflammatory responses, responsible for many of the systemic manifestations during the inflammatory process. Thus, inhibition of TNFα, is a commonplace practice in the treatment of these disorders. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.9b00036
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http://dx.doi.org/10.1021/acschemneuro.9b00036DOI Listing
April 2019
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APH-1A component of γ-secretase forms an internal water and ion-containing cavity.

ACS Chem Neurosci 2019 Apr 12. Epub 2019 Apr 12.

Anterior pharynx-defective 1A (APH-1A) is a seven transmembrane component of γ-secretase (GS), an aspartyl protease enzyme involved in the production of toxic amyloid-β peptides in Alzheimer's disease patients. Cryo-electron microscopy structures of the enzyme complex revealed a central cavity its APH-1A component, similar to water-containing cavities in G-protein coupled receptors (GPCRs). In this work, we performed molecular dynamics and umbrella sampling simulations to understand the role of APH-1A cavity in the GS complex. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00150DOI Listing

A Neuroleptic drug targets Brain-eating Amoeba: Effects of Promethazine on Neurotropic Acanthamoeba castellanii.

ACS Chem Neurosci 2019 Apr 12. Epub 2019 Apr 12.

Acanthamoeba spp. has recently been reported to express diverse group of ion-channels and receptors that are expressed by human cells which bind drugs that are used in non-infectious diseases. Bioinformatics computational tools, growth assays and 3D structural modeling has enabled the discovery of primitive muscarinic receptors, voltage gated calcium channels and transport pumps like Na-K ATPase in this protist pathogen. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00100DOI Listing
April 2019
2 Reads

Targeted Manipulation of Brain Serotonin - RNAi-mediated Knockdown of Tryptophan hydroxylase 2 in Rats.

ACS Chem Neurosci 2019 Apr 12. Epub 2019 Apr 12.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme in the biosynthesis of the biogenic monoamine serotonin (5-hydroxytryptamine, 5-HT). Two existing TPH isoforms are responsible for the generation of two distinct serotonergic systems in vertebrates. TPH1, predominantly expressed in gastrointestinal tract and pineal gland, mediates 5-HT biosynthesis in non-neuronal tissues, while TPH2, mainly found in the raphe nuclei of the hindbrain, is accountable for the production of 5-HT in the brain. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00635DOI Listing
April 2019
1 Read

Nitration and glycation diminish the α-synuclein role on the formation and scavenging of Cu-catalyzed reactive oxygen species.

ACS Chem Neurosci 2019 Apr 11. Epub 2019 Apr 11.

Human α-synuclein is a small monomeric protein (140 residues) essential to maintain the function of the dopaminergic neurons and the neuronal redox balance. However, it holds a dark side since it is able to clump inside the neurons forming insoluble aggregates known as Lewy bodies, which are considered the hallmark of Parkinson's disease. Sporadic mutations and non-enzymatic post-translational modifications are well-known to stimulate the formation of Lewy bodies. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00142DOI Listing

Development and Evaluation of Two Potential 5-HT7 Receptor PET Tracers: [18F]ENL09 and [18F]ENL10.

ACS Chem Neurosci 2019 Apr 11. Epub 2019 Apr 11.

The latest addition to the serotonin (5-HT) receptor family is the 5-HT7 receptor (5-HT7R). This receptor has gained interest as a drug target due to its involvement in various disorders such as depression or schizophrenia. There is currently no clinically validated positron emission tomography (PET) tracer for the 5-HT7R available. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.9b00132
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http://dx.doi.org/10.1021/acschemneuro.9b00132DOI Listing
April 2019
2 Reads

trans-Cinnamic acid conjugated gold nanoparticles as potent therapeutics against brain-eating amoeba Naegleria fowleri.

ACS Chem Neurosci 2019 Apr 10. Epub 2019 Apr 10.

Primary amebic meningoencephalitis (PAM), a deadly brain infection is caused by brain-eating amoeba Naegleria fowleri. The current first line of treatment against PAM is a mixture of amphotericin B, rifampin and miltefosine. Since, no single effective drug has been developed so far, the mortality rate is above 95 %. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00111DOI Listing
April 2019
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Palmitoylation by multiple DHHC enzymes enhances dopamine transporter function and stability.

ACS Chem Neurosci 2019 Apr 9. Epub 2019 Apr 9.

The dopamine transporter (DAT) is a plasma membrane protein that mediates the reuptake of extracellular dopamine (DA) and controls the spatiotemporal dynamics of dopaminergic neurotransmission. The transporter is subject to fine control that tailors clearance of transmitter to physiological demands, and dysregulation of reuptake induced by psychostimulant drugs, transporter polymorphisms, and signaling defects may impact transmitter tone in disease states. We previously demonstrated that DAT undergoes complex regulation by palmitoylation, with acute inhibition of the modification leading to rapid reduction of transport activity, and sustained inhibition of the modification leading to transporter degradation and reduced expression. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.8b00558
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http://dx.doi.org/10.1021/acschemneuro.8b00558DOI Listing
April 2019
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5-HT Receptor-Mediated Activation of ERK1/2 Requires Both Gα and β-Arrestin Proteins.

ACS Chem Neurosci 2019 Apr 4. Epub 2019 Apr 4.

5-HT receptors modulate synaptic serotonin (5-HT) levels and play a significant role in the regulation of emotional behaviors. These receptors are Gα-coupled and inhibit adenylyl cyclase but have also been reported to activate MAP kinases; however, the details of signaling cascades downstream of 5-HT receptor activation remain unclear, particularly in neuronal cells. We generated a stable 5-HT receptor-expressing Neuro2A (N2A-1B) neuronal cell line and demonstrate that activation of these receptors by the selective 5-HT agonist CP-94253 results in activation of ERK1/2 but not of other closely related MAP kinases. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.8b00596
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http://dx.doi.org/10.1021/acschemneuro.8b00596DOI Listing
April 2019
1 Read

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.

ACS Chem Neurosci 2019 Apr 4. Epub 2019 Apr 4.

No universally efficacious therapy exists for chronic pain, a disease affecting one-fifth of the global population. An overreliance in 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 non-addictive treatment options. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00166DOI Listing
April 2019
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Novel Quinolylnitrones Combining Neuroprotective and Antioxidant Properties.

ACS Chem Neurosci 2019 Apr 9. Epub 2019 Apr 9.

Institute of General Organic Chemistry (CSIC) , Juan de la Cierva 3 , Madrid 28006 , Spain.

We describe here the preparation, neuroprotective analysis, and antioxidant capacity of 11 novel quinolylnitrones (QN). The neuroprotective analysis of QN1-11 in an oxygen-glucose deprivation model, in primary neuronal cultures, has been determined, allowing us to identify QN6 as a very potent neuroprotective agent, showing significant high value at 0.5 and 10 μM (86. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00152DOI Listing

Enolase1 Alleviates Cerebral Ischemia-Induced Neuronal Injury via Its Enzymatic Product Phosphoenolpyruvate.

ACS Chem Neurosci 2019 Apr 16. Epub 2019 Apr 16.

Shenzhen Research Institute , Hunan University , Shenzhen , Guangdong 518000 , China.

Stroke is a leading cause of disability and the second leading cause of death among adults worldwide, while the mechanisms underlying neuronal death and dysfunction remain poorly understood. Here, we investigated the differential proteomic profiles of mouse brain homogenate with 3 h of middle cerebral artery occlusion (MCAO) ischemia, or sham, using Coomassie Brilliant Blue staining, followed by mass spectrometry. We identified enolase1 (ENO1), a key glycolytic enzyme, as a potential mediator of neuronal injury in MCAO ischemic model. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00103DOI Listing
April 2019
9 Reads

Functional Coupling of K+-Cl- Cotransporter (KCC) to GABA-Gated Cl- Channels in the Central Nervous System of Drosophila melanogaster leads to altered drug sensitivities.

ACS Chem Neurosci 2019 Apr 3. Epub 2019 Apr 3.

GABAergic signaling is the cornerstone for fast synaptic inhibition of neural signaling in arthropods and mammals and is the molecular target for insecticides and pharmaceuticals, respectively. The K+-Cl- cotransporter (KCC) is the primary mechanism by which mature neurons maintain low intracellular Cl- concentration, yet the fundamental physiology, comparative physiology, and toxicological relevance of insect KCC is understudied. Considering this, we employed electrophysiological, genetic, and pharmacological methods to characterize the physiological underpinnings of KCC function to the Drosophila CNS. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00697DOI Listing

DCPIB, an Inhibitor of Volume-Regulated Anion Channels, Distinctly Modulates K2P Channels.

ACS Chem Neurosci 2019 Apr 17. Epub 2019 Apr 17.

Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences , Southern Medical University , Guangzhou 510515 , China.

K2P potassium channels stabilize the resting membrane potential in nearly all cells and have been implicated in several neuronal, cardiovascular, and immune diseases. DCPIB, a known specific and potent inhibitor of volume-regulated anion channels (VRAC), has been reported to activate TREK1 and TREK2 in astrocytes and in vitro recently. In the present study, we demonstrated DCPIB also voltage dependently activated TRAAK besides TREK1/TREK2, showing DCPIB activated all TREK subfamily members. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00010DOI Listing

Impact of Gold Nanoparticles on Amyloid β-Induced Alzheimer's Disease in a Rat Animal Model: Involvement of STIM Proteins.

ACS Chem Neurosci 2019 Apr 1. Epub 2019 Apr 1.

Department of Toxicology & Pharmacology, Faculty of Pharmacy; Toxicology and Poisoning Research Centre , Tehran University of Medical Sciences , Tehran 1416753955 , Iran.

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aβ) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aβ fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00622DOI Listing
April 2019
4.362 Impact Factor

Shared Behavioral and Neurocircuitry Disruptions in Drug Addiction, Obesity, and Binge Eating Disorder: Focus on Group I mGluRs in the Mesolimbic Dopamine Pathway.

ACS Chem Neurosci 2019 Apr 15. Epub 2019 Apr 15.

Department of Pharmacology, Vanderbilt Center for Addiction Research , Vanderbilt University , Nashville , Tennessee 37232 , United States.

Accumulated data from clinical and preclinical studies suggest that, in drug addiction and states of overeating, such as obesity and binge eating disorder (BED), there is an imbalance in circuits that are critical for motivation, reward saliency, executive function, and self-control. Central to these pathologies and the extensive topic of this Review are the aberrations in dopamine (DA) and glutamate (Glu) within the mesolimbic pathway. Group I metabotropic glutamate receptors (mGlus) are highly expressed in the mesolimbic pathway and are poised in key positions to modulate disruptions in synaptic plasticity and neurotransmitter release observed in drug addiction, obesity, and BED. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00601DOI Listing
April 2019
1 Read

N-Methyl-4-phenylpyridinium Scaffold-Containing Lipophilic Compounds Are Potent Complex I Inhibitors and Selective Dopaminergic Toxins.

ACS Chem Neurosci 2019 Apr 10. Epub 2019 Apr 10.

Department of Chemistry , Wichita State University , Wichita , Kansas 67260 , United States.

Although the exact cause or causes of Parkinson's disease (PD) are not fully understood, it is believed that environmental factors play a major role. The discovery that a synthetic chemical, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-derived N-methyl-4-phenylpyridinium (MPP), recapitulates major pathophysiological characteristics of PD in humans has provided the strongest support for this possibility. While the mechanism of the selective dopaminergic toxicity of MPP has been extensively studied and is, in most respects, well accepted, several key aspects of the mechanism are still debatable. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00184DOI Listing

Serotonin 5-HT Receptor Biased Agonists Display Differential Anxiolytic Activity in a Rat Social Interaction Model.

ACS Chem Neurosci 2019 Apr 2. Epub 2019 Apr 2.

Pierre Fabre Laboratories , Castres 81100 , France.

When placed in an unfamiliar and brightly lit open-field, two adult male rats that have not previously interacted display a low level of social interaction (SI) attributed to an anxiety-like state. The SI test has therefore been used to explore anxiolytic/antistress activity. Here, we investigated the effects of serotonin 5-HT receptor agonists displaying various activity profiles, i. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.8b00661
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http://dx.doi.org/10.1021/acschemneuro.8b00661DOI Listing
April 2019
3 Reads

Prolines Affect the Nucleation Phase of Amyloid Fibrillation Reaction; Mutational Analysis of Human Stefin B.

ACS Chem Neurosci 2019 Apr 9. Epub 2019 Apr 9.

Jožef Stefan International Postgraduate School , Jamova 39 , 1000 Ljubljana , Slovenia.

Proline residues play a prominent role in protein folding and aggregation. We investigated the influence of single prolines and their combination on oligomerization and the amyloid fibrillation reaction of human stefin B (stB). The proline mutants influenced the distribution of oligomers between monomers, dimers, and tetramers as shown by the size-exclusion chromatography. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00621DOI Listing

Dissecting the Catecholamines: How New Approaches Will Facilitate the Distinction between Noradrenergic and Dopaminergic Systems.

ACS Chem Neurosci 2019 Apr 28;10(4):1872-1874. Epub 2019 Mar 28.

To overcome the limitations of fast scan cyclic voltammetry (FSCV) to discriminate between catecholamines, we discuss new approaches to monitor the dynamics of these neurochemicals with high spatial, genetic, and temporal specificity. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00157DOI Listing

Insight into Novel Treatment for Cognitive Dysfunctions across Disorders.

ACS Chem Neurosci 2019 Mar 28. Epub 2019 Mar 28.

Campbell Family Mental Health Research Institute , Centre for Addiction and Mental Health , Toronto , ON M5T 1R8 , Canada.

Cognitive dysfunctions, including impaired attention, learning, memory, and problem solving, occur in psychiatric diseases, such as depression, and are a hallmark of aging. Altered GABAergic signaling is similarly reported across these conditions, but therapeutic approaches are limited by pan-receptor activities of benzodiazepine-like ligands. α5-GABA-A receptor-preferring ligands uncover novel therapeutics for cognitive dysfunctions. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00148DOI Listing

Interplay between Mitophagy and Inflammasomes in Neurological Disorders.

ACS Chem Neurosci 2019 Apr 8. Epub 2019 Apr 8.

Department of Pharmacology and Toxicology , National Institute of Pharmaceutical Education and Research (NIPER) , Ahmedabad, Gandhinagar - 382 355 , Gujarat , India.

Mitophagy and inflammasomes have a pivotal role in the development of neuropathology. Molecular mechanisms behind mitophagy and inflammasomes are well-understood, but lacunae prevail in understanding the crosstalk between them in various neurological disorders. As mitochondrial dysfunction is the prime event in neurodegeneration, the clearance of impaired mitochondria is one of the main tasks for maintaining cell integrity in the majority of neuropathologies. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00117DOI Listing

Binding of Noradrenaline to Native and Intermediate States during the Fibrillation of α-Synuclein Leads to the Formation of Stable and Structured Cytotoxic Species.

ACS Chem Neurosci 2019 Apr 9. Epub 2019 Apr 9.

School of Biotechnology , Jawaharlal Nehru University , New Delhi 110067 , India.

Parkinson's disease is characterized by the deterioration of dopaminergic neurons of substantia nigra pars compacta along with a substantial loss of noradrenergic neurons of the locus coeruleus, which is the major source of noradrenaline (NA) in the brain. We have investigated the interaction of NA with α-synuclein (α-syn), the major protein constituent of Lewy bodies that are the pathological hallmark of Parkinson's disease (PD). It is expected that NA, like dopamine, could bind to α-syn and modulate its aggregation propensity and kinetics, which could also contribute to the onset of PD. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00650DOI Listing
April 2019
2 Reads
4.362 Impact Factor

Molecular Simulations Reveal Terminal Group Mediated Stabilization of Helical Conformers in Both Amyloid-β42 and α-Synuclein.

ACS Chem Neurosci 2019 Apr 5. Epub 2019 Apr 5.

Department of Physics, Bernal Institute , University of Limerick , Limerick V94 T9PX , Ireland.

The presence of partially structured helices in natively unfolded amyloid-β42 (Aβ42) and α-synuclein (αS) has been shown to accelerate fibrillation in the onset of Alzheimer's and Parkinson's disease, respectively. At the other extreme, folded stable helical conformers have also been reported to resist amyloid formation. Recent studies indicate that amyloidogenic aggregation can be impeded using small molecules that stabilize the α-helical monomers and switch off the neurotoxic pathway. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00053DOI Listing
April 2019
4.362 Impact Factor

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

ACS Chem Neurosci 2019 Apr 12. Epub 2019 Apr 12.

Laboratory of Molecular Neurobiology, Biomedical Research Institute (BIOMED) , UCA-CONICET , Av. Alicia Moreau de Justo 1600 , C1107AFF Buenos Aires , Argentina.

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, nAChRs contribute to the pathological mechanisms of neurodegenerative disorders, such as Alzheimer and Parkinson diseases. In the peripheral nerve-muscle synapse, the vertebrate neuromuscular junction, "classical" myasthenia gravis (MG) and other forms of neuromuscular transmission disorders are antibody-mediated autoimmune diseases. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00041DOI Listing
April 2019
1 Read

Asthmatic Augmentation of Airway Vagal Activity Involves Decreased Central Expression and Activity of CD73 in Rats.

ACS Chem Neurosci 2019 Apr 5. Epub 2019 Apr 5.

Department of Neurobiology, School of Basic Medical Sciences , Fudan University , Shanghai 200032 , China.

The severity of asthma is closely related to the intensity of airway vagal activity; however, it is unclear how airway vagal activity is centrally augmented in asthma. Here we report that in an asthma model of male Sprague-Dawley rats, the expression and activity of ecto-5'-nucleotidase (CD73) were decreased in airway vagal centers, ATP concentration in cerebral spinal fluid was increased, and the inhibitory and excitatory airway vagal responses to intracisternally injected ATP (5 μmol) and CD73 inhibitor AMPCP (5 μmol), respectively, were attenuated. In airway vagal preganglionic neurons (AVPNs) identified in medullary slices of neonatal Sprague-Dawley rats, AMPCP (100 μmol·L) caused excitatory effects, as are shown in patch-clamp by depolarization, increased neuronal discharge, and facilitated spontaneous excitatory postsynaptic currents (sEPSCs). Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.9b00023
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http://dx.doi.org/10.1021/acschemneuro.9b00023DOI Listing
April 2019
8 Reads

Discovery of δ Opioid Receptor Full Inverse Agonists and Their Effects on Restraint Stress-Induced Cognitive Impairment in Mice.

ACS Chem Neurosci 2019 Apr 1. Epub 2019 Apr 1.

Laboratory of Medicinal Chemistry, School of Pharmacy , Kitasato University , 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641 , Japan.

The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than that of a reference compound ICI-174,864. Intraperitoneal administration of SYK-657 induced the short-term memory improving effect in mice without abnormal behaviors. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00067DOI Listing
April 2019
2 Reads

WIN 55,212-2 Reverted Pilocarpine-Induced Status Epilepticus Early Changes of the Interaction among 5-HT/NMDA/CB Receptors in the Rat Hippocampus.

ACS Chem Neurosci 2019 Mar 26. Epub 2019 Mar 26.

Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery , University of Malta , Msida MSD 2080 , Malta.

The molecular basis for temporal lobe epileptogenesis  remains poorly defined. Recent evidence shows that serotonin 2C receptors (5-HTRs), NR2A and NR2B subunit-containing N-methyl-d-aspartate receptors (NMDARs) and cannabinoid 1 receptors (CBRs) may be involved in the progression of the epileptic disorders. Moreover, CBR activation has been reported to modulate the activity of 5-HT and NMDA receptors. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00080DOI Listing
March 2019
1 Read

Therapeutic Potential of Polyamidoamine Dendrimer for Amyloidogenic Transthyretin Amyloidosis.

ACS Chem Neurosci 2019 Mar 26. Epub 2019 Mar 26.

Program for Leading Graduate Schools 'Health Life Science: Interdisciplinary and Glocal Oriented (HIGO) Program' , Kumamoto University , Kumamoto 860-8555 , Japan.

Amyloidogenic transthyretin (ATTR) amyloidosis is caused by a formation of ATTR amyloid fibrils. Because ATTR misfolding triggers the formation of aggregates and amyloid fibrils, which are considered to deposit on the tissues, novel clinically effective therapeutic strategies targeted to those processes are urgently needed. In this study, to discover a new drug candidate for ATTR amyloidosis therapy, we focused on polyamidoamine dendrimer (dendrimer), a 3D-structural nanomaterial, which has a branched cationic polymer repeating polyamidoamine units. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00059DOI Listing

Dual 5-HT and D Receptor Antagonists in a Group of 1 H-Pyrrolo[3,2- c]quinolines with Neuroprotective and Procognitive Activity.

ACS Chem Neurosci 2019 Apr 2. Epub 2019 Apr 2.

IGF , Université de Montpellier , CNRS INSERM , 34094 Montpellier , France.

In light of the multifactorial origin of neurodegenerative disorders and some body of evidence indicating that pharmacological blockade of serotonin 5-HT and dopamine D receptors might be beneficial for cognitive decline, we envisioned ( S)-1-[(3-chlorophenyl)sulfonyl]-4-(pyrrolidine-3-yl-amino)-1 H-pyrrolo[3,2- c]quinoline (CPPQ), a neutral antagonist of 5-HTR, as a chemical template for designing dual antagonists of 5-HT/D receptors. As shown by in vitro experiments, supported by quantum chemical calculations and molecular dynamic simulations, introducing alkyl substituents at the pyrrolidine nitrogen of CPPQ, fulfilled structural requirements for simultaneous modulation of 5-HT and D receptors. The study identified compound 19 (( S)-1-((3-chlorophenyl)sulfonyl)- N-(1-isobutylpyrrolidin-3-yl)-1 H-pyrrolo[3,2- c]quinolin-4-amine), which was classified as a dual 5-HT/DR antagonist ( K = 27 nM, K = 7 nM). Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00618DOI Listing

Large Intracellular Domain-Dependent Effects of Positive Allosteric Modulators on Glycine Receptors.

ACS Chem Neurosci 2019 Mar 29. Epub 2019 Mar 29.

Departamento de Fisiologı́a, Facultad de Ciencias Biológicas , Universidad de Concepción , Chile.

Glycine receptors (GlyRs) are members of the pentameric ligand-gated ionic channel family (pLGICs) and mediate fast inhibitory neurotransmission in the brain stem and spinal cord. The function of GlyRs can be modulated by positive allosteric modulators (PAMs). So far, it is largely accepted that both the extracellular (ECD) and transmembrane (TMD) domains constitute the primary target for many of these PAMs. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00050DOI Listing
March 2019
1 Read

Extracellular ATP Regulates the Vesicular Pore Opening in Chromaffin Cells and Increases the Fraction Released During Individual Exocytosis Events.

ACS Chem Neurosci 2019 Apr 1. Epub 2019 Apr 1.

Department of Chemistry and Molecular Biology , University of Gothenburg , Kemivägen 10 , 41296 Gothenburg , Sweden.

Adenosine triphosphate (ATP) is the main energy source for cellular metabolism. Besides that, ATP is a neurotransmitter and a cotransmitter that acts on purinergic receptors present either pre- or postsynaptically. Almost all types of secretory vesicles from any neuron or animal species contain high concentrations of ATP, being an essential factor in the accumulation of neurotransmitters. Read More

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http://dx.doi.org/10.1021/acschemneuro.8b00722DOI Listing

In This Issue, Volume 10, Issue 3.

ACS Chem Neurosci 2019 Mar;10(3):1117

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http://dx.doi.org/10.1021/acschemneuro.9b00130DOI Listing

Dysregulation of Myosin Complex and Striated Muscle Contraction Pathway in the Brains of ALS-SOD1 Model Mice.

ACS Chem Neurosci 2019 Mar 28. Epub 2019 Mar 28.

Key Laboratory of Modern Toxicology of Shenzhen , Institute of Toxicology, Shenzhen Center for Disease Control and Prevention , Shenzhen 518055 , China.

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by cortical and spinal motor neuron degeneration, some inherited cases of which are caused by mutations in the gene coding for copper-zinc superoxide dismutase-1 (SOD1). The SOD1 mutant model mouse, which expresses large amounts of mutant SOD1, develops adult-onset neurodegeneration of spinal motor neurons and progressive motor deficits leading to paralysis. We used the Tandem Mass Tag technique to investigate the proteome profile of hippocampus, cerebral cortex, and medulla oblongata of the SOD1 mutant model mice as compared with that of wild-type (WT) mice. Read More

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http://pubs.acs.org/doi/10.1021/acschemneuro.8b00704
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http://dx.doi.org/10.1021/acschemneuro.8b00704DOI Listing
March 2019
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Ischemic Postconditioning Recovers Cortex Ascorbic Acid during Ischemia/Reperfusion Monitored with an Online Electrochemical System.

ACS Chem Neurosci 2019 Mar 27. Epub 2019 Mar 27.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems , Institute of Chemistry, the Chinese Academy of Sciences (CAS), CAS Research/Education Center for Excellence in Molecule Science , Beijing 100190 , China.

As a promising therapeutic treatment, ischemic postconditioning has recently received considerable attention. Although the neuroprotection effect of postconditioning has been observed, a reliable approach that can evaluate the neuroprotective efficiency of postconditioning treatment during the acute period after ischemia remains to be developed. This study investigates the dynamics of cortex ascorbic acid during the acute period of cerebral ischemia before and after ischemic postconditioning with an online electrochemical system (OECS). Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00056DOI Listing