2,363 results match your criteria ACS chemical neuroscience[Journal]


Role of Membrane Tension Sensitive Endocytosis and Rho GTPases in the Uptake of the Alzheimer's Disease Peptide Aβ(1-42).

ACS Chem Neurosci 2020 Jun 4. Epub 2020 Jun 4.

Intraneuronal accumulation of amyloid-β (Aβ) is an early pathological signum of Alzheimer's disease, and compartments of the endolysosomal system have been implicated in both seeding and cell-cell propagation of Aβ aggregation. We have studied how clathrin-independent mechanisms contribute to Aβ endocytosis, exploring pathways that are sensitive to changes in membrane tension and the regulation of Rho GTPases. Using live cell confocal microscopy and flow cytometry, we show uptake of monomeric Aβ(1-42) into endocytic vesicles and vacuole-like dilations, following relaxation of osmotic pressure-induced cell membrane tension. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00053DOI Listing

The glymphatic system visualized by chemical-exchange-saturation-transfer MRI.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Dysfunction of the glymphatic system may play a significant role in the development of neurodegenerative diseases. However, in vivo imaging of the glymphatic system is challenging. In this study, we describe an unconventional MRI method for imaging the glymphatic system based on chemical exchange saturation transfer, which we tested in an in vivo porcine model of impaired glymphatic function. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00222DOI Listing

Comparison of Synthetic Neuronal Model Membrane Mimics in Amyloid Aggregation at Atomic Resolution.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Alzheimer's disease (AD) is a severe neurodegenerative disorder caused by abnormal accumulation of toxic amyloid plaques of the amyloid-beta (Aβ) or the tau proteins in the brain. The plaque deposition leading to the collapse of the cellular integrity is responsible for a myriad of surface phenomena acting at the neuronal lipid interface. Recent years have witnessed dysfunction of the blood-brain barriers (BBB) associated with AD. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00166DOI Listing

SARS-CoV-2 more than a respiratory virus: Its potential role in neuropathogenesis.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Coronavirus disease-19 (COVID-19) pandemic has emerged as one of the major outbreaks to be mentioned in history in coming times. Like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a respiratory virus infecting the lungs with fever, dry cough and acute pneumonia being the major symptoms. It infects the epithelial cells expressing Angiotensin converting enzyme 2 (ACE2) receptor, which is crucial for the viral entry. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00251DOI Listing

Novel oral nanoparticle formulation of sustained release naloxone with mild withdrawal symptoms in mice.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Chronic use of opioids can lead to tolerance, dependence, abuse, and addiction. This in turn can result in dose escalation and opioid overdose. Opioid overdose can be fatal due to severe opioid-induced respiratory depression (OIRD). Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00141DOI Listing

Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation during the COVID-19 Outbreak.

ACS Chem Neurosci 2020 Jun 2. Epub 2020 Jun 2.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha 410008, P. R. China.

The coronavirus disease 19 (COVID-19) pandemic has brought a great threat to global public health. Currently, mounting evidence has shown the occurrence of neurological symptoms in patients with COVID-19. However, the detailed mechanism by which the SARS-CoV-2 attacks the brain is not well characterized. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00294DOI Listing

Myelin Associated Inhibitory Proteins as a Therapeutic Target for Healing of CNS Injury.

ACS Chem Neurosci 2020 Jun 2. Epub 2020 Jun 2.

Department of Bioscience & Bioengineering, Indian Institute of Technology Jodhpur, NH 65, Surpura Bypass Road, Karwar, Rajasthan 342037, India.

The labyrinth of intricate circuitry makes the central nervous system quite inept to regenerate its functionality after a devastating injury. Apart from targeting the major inhibitory effect of glial scar associated proteoglycans like chondroitin sulfate and the reactive glial cell secreted inflammatory and growth inhibitory molecules, the other major regeneration stalling component that arises after severe CNS injury is myelin and its associated proteinaceous debris comprising myelin-associated glycoprotein (MAG), neurite outgrowth inhibitor protein (NOGO), and oligodendrocyte myelin glycoprotein (OMgp). Various experiments revealed that, upon neutralization of those myelin inhibitors, regeneration could occur satisfactorily. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00280DOI Listing

Ruthenium-Mediated F-Fluorination and Preclinical Evaluation of a New CB Receptor Imaging Agent [F]FPATPP.

ACS Chem Neurosci 2020 Jun 1. Epub 2020 Jun 1.

Cannabinoid receptor 1 (CB1R) controls various physiological and pathological conditions, including memory, motivation, and inflammation and is thus an interesting target for positron emission tomography (PET). Herein, we report a ruthenium-mediated radiolabeling synthesis and preclinical evaluation of a new CB1R specific radiotracer, [F]FPATPP. [F]FPATPP was produced with 16. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00313DOI Listing

Multitargeted Compounds Derived from (2,5-Dioxopyrrolidin-1-yl)(phenyl)-Acetamides as Candidates for Effective Anticonvulsant and Antinociceptive Agents.

ACS Chem Neurosci 2020 Jun 1. Epub 2020 Jun 1.

We developed a focused set of original hybrid pyrrolidine-2,5-dione derivatives with potent anticonvulsant and antinociceptive properties. These hybrid compounds demonstrated broad-spectrum protective activity in a range of mouse models, such as the maximal electroshock (MES) test, the pentylenetetrazole-induced seizures (scPTZ), and the 6 Hz (32 mA) seizures. Compound 22 showed the most potent anticonvulsant activity (ED50 MES = 23. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00257DOI Listing

Tumor necrosis factor-alpha, the pathological key of post-traumatic epilepsy: A comprehensive systematic review.

ACS Chem Neurosci 2020 Jun 1. Epub 2020 Jun 1.

Post-traumatic epilepsy (PTE) is one of the detrimental outcomes of traumatic brain injury (TBI), resulting in recurrent seizures which impact daily life. However, the pathological relationship between PTE and TBI remains unclear, and commonly prescribed anti-epileptic drugs (AED) are ineffective against PTE. Fortunately, emerging research implicates neuroinflammation particularly the tumor necrosis factor-alpha (TNFα) as the key mediator for PTE development. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00301DOI Listing
June 2020
4.362 Impact Factor

Heralding Healthcare Professionals: Recognition of Neurological Deficits in COVID-19.

ACS Chem Neurosci 2020 May 29. Epub 2020 May 29.

Mount Auburn Hospital, Boston Urogynecology Associates, Cambridge, Massachusetts 02138, United States.

The 2019 novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic disease that is dominated by pulmonary symptoms. However, recent reports of isolation of the virus from cerebrospinal fluid (CSF) coupled with radiological evidence of zones of necrosis in the brain, have elucidated the neurotropic potential of SARS-CoV-2. The acute respiratory failure seen in patients with COVID-19 is alarming and could be due to the effects of SARS-CoV-2 on the central respiratory regulatory centers in the brainstem. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00286DOI Listing

Solid lipid nanoparticles enhanced the neuroprotective role of curcumin against epilepsy through activation of Bcl-2 family and P38 MAPK pathway.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Oxidative stress of neurons caused by a series of complex neuropathological processes, will induce certain neurodegenerative disorders including epilepsy. Curcumin (Cur) is an effective natural anti-oxidant compound, however, the poor bioavailability obstructs its neural protective applications. In this study, Cur is encapsulated in solid lipid nanoparticles (SLNs) for better neuroprotective efficacy. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00242DOI Listing

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Kinases are highly tractable drug targets that have reached unparalleled success in fields such as cancer but whose potential has not yet been realized in neuroscience. There are currently 55 approved small molecule kinase-targeting drugs, 48 of which have an anti-cancer indication. The intrinsic complexity linked to central nervous system (CNS) drug development and a lack of validated targets has hindered progress in developing kinase inhibitors for CNS disorders when compared to other therapeutic areas such as oncology. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00176DOI Listing

Time Will Tell the Utility of Biomarkers.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, United States.

A biomarker, such as protein accumulation as an indicator of disease, can be used to predict disease manifestation, determine intervention, and monitor treatment efficacy. Biomarker development frequently focuses on early detection of disease as this is typically considered the only or most pressing need. However, the ideal time point for biomarker use may not always be early in disease but instead, as we will discuss, could be when enough information is available to predict the association between biomarker (protein accumulation) and disease manifestation (symptom severity, progression, prognosis). Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00238DOI Listing

Effects of Disulfide Bonds on Bindings of Inhibitors to BACE1 Decoded by Multiple Replica Accelerated Molecular Dynamics Simulations.

ACS Chem Neurosci 2020 May 27. Epub 2020 May 27.

The β-amyloid cleaving enzyme 1 (BACE1) has been thought as an efficient target for treatment of Alzheimer's disease (AD). Deep insight into inhibitor-BACE1 binding mechanism is of significance for design of potent drugs toward BACE1. In this work, multiple replica accelerated molecular dynamics (MR-aMD) simulations, principal component (PC) analysis and free energy landscapes were integrated to decode effect of disulfide bonds (SSBs) in BACE1 on bindings of three inhibitors 3KO, 3KT and 779 to BACE1. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00234DOI Listing

Immunity-Boosting Spices and the Novel Coronavirus.

ACS Chem Neurosci 2020 May 26. Epub 2020 May 26.

Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates.

Although there is no reported genetic predisposition in contracting coronavirus disease 2019 (COVID-19), the mortality rate varies among different ethnic groups. Here we determined potential correlation between COVID-19 and spice consumption. The data from 163 countries including total cases, total deaths, and total recovered were analyzed. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00239DOI Listing

Green Tea Extracts EGCG and EGC Display Distinct Mechanisms in Disrupting Aβ Protofibril.

ACS Chem Neurosci 2020 May 22. Epub 2020 May 22.

The amyloid beta (Aβ) fibrillar aggregate is the hallmark of Alzheimer's disease (AD). Disassembling preformed fibril or inhibiting Aβ aggregation is considered as a therapeutic strategy for AD. Increasing evidence shows that green tea extracts, epigallocatechin-3-gallate (EGCG, containing an extra gallic acid ester group compared to EGC) and epigallocatechin (EGC), can disassociate Aβ fibrils and attenuate Aβ toxicity. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00277DOI Listing

Resveratrol Differently Modulates Group I Metabotropic Glutamate Receptors Depending on Age in SAMP8 Mice.

ACS Chem Neurosci 2020 Jun 4. Epub 2020 Jun 4.

Department of Inorganic and Organic Chemistry and Biochemistry, Faculty of Chemical Sciences and Technologies, Faculty of Medicine of Ciudad Real, Regional Center of Biomedical Research, University of Castilla-La Mancha, Ciudad Real 13071, Spain.

Glutamate homeostasis is critical for neurotransmission as this excitatory neurotransmitter has a relevant role in cognition functions through ionotropic and metabotropic glutamate receptors in the central nervous system. During the last years, the role of the group I metabotropic glutamate receptors (mGluRs) in neurodegenerative diseases such as Alzheimer's disease has been intensely investigated. Resveratrol (RSV) is a natural polyphenolic compound that is thought to have neuroprotective properties for human health. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00067DOI Listing

The ionotropic glutamate receptor GluA2 in complex with bicyclic pyrimidinedione-based compounds: when small compound modifications have distinct effects on binding interactions.

ACS Chem Neurosci 2020 May 21. Epub 2020 May 21.

AMPA receptors comprise an important class of ionotropic glutamate receptors activated by glutamate in the central nervous system. These receptors have been shown to be involved in brain diseases, e.g. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00195DOI Listing

Bryostatin 1 Promotes Synaptogenesis and Reduces Dendritic Spine Density in Cortical Cultures through a PKC-Dependent Mechanism.

ACS Chem Neurosci 2020 Jun 21;11(11):1545-1554. Epub 2020 May 21.

Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States.

The marine natural product bryostatin 1 has demonstrated procognitive and antidepressant effects in animals and has been entered into human clinical trials for treating Alzheimer's disease (AD). The ability of bryostatin 1 to enhance learning and memory has largely been attributed to its effects on the structure and function of hippocampal neurons. However, relatively little is known about how bryostatin 1 influences the morphology of cortical neurons, key cells that also support learning and memory processes and are negatively impacted in AD. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00175DOI Listing

Classics in Chemical Neuroscience: Baclofen.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Warren Center for Neuroscience Drug Discovery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States.

Baclofen, β-(4-chlorophenyl)-γ-aminobutyric acid, holds a unique position in neuroscience, remaining the only U.S. Food and Drug Administration (FDA) approved GABA agonist. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00254DOI Listing

Proposed Intranasal Route for Drug Administration in the Management of Central Nervous System Manifestations of COVID-19.

ACS Chem Neurosci 2020 06 20;11(11):1523-1524. Epub 2020 May 20.

Department of Biology, Chemistry and Environmental Sciences, College of Arts and Sciences, American University of Sharjah, University City, Sharjah, United Arab Emirates.

There is mounting evidence of the central nervous system manifestations associated with COVID-19, particularly in severe cases. Up to 25% of COVID-19 cases exhibit neurological manifestations associated with COVID-19. In view of the devastating nature of the disease due to severe acute respiratory syndrome coronavirus 2, here we debate intranasal drug delivery, in addition to intravenous delivery, as a therapeutic strategy in the management of COVID-19 cases with central nervous system involvement. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00288DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241733PMC

NeuroChat with Dr. Karen Gregory.

ACS Chem Neurosci 2020 May;11(10):1373-1375

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http://dx.doi.org/10.1021/acschemneuro.0c00183DOI Listing

Autonomic Brain Centers and Pathophysiology of COVID-19.

ACS Chem Neurosci 2020 06 19;11(11):1520-1522. Epub 2020 May 19.

Bioengineering Laboratory, Faculty of Sciences and Techniques, Sultan Moulay Slimane University, 23000 Beni Mellal, Morocco.

Accumulating data have now shown strong evidence that COVID-19 infection leads to the occurrence of neurological signs with different injury severity. Anosmia and agueusia are now well documented and included in the criteria list for diagnosis, and specialists have stressed that doctors screen COVID-19 patients for these two signs. The eventual brainstem dysregulation, due to the invasion of SARS CoV-2, as a cause of respiratory problems linked to COVID-19, has also been extensively discussed. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241734PMC

PyrPeg, a Blood-Brain-Barrier-Penetrating Two-Photon Imaging Probe, Selectively Detects Neuritic Plaques, Not Tau Aggregates.

ACS Chem Neurosci 2020 Jun 2. Epub 2020 Jun 2.

KU-KIST Graduate School of Converging Science and Technology, Korea University, 145 Anam-ro, Seongbuk-gu, Seoul 02841, Republic of Korea.

Amyloid-β (Aβ) tracers have made a significant contribution to the treatment of Alzheimer's disease (AD) by allowing a definitive diagnosis in living patients. Unfortunately, they also detect tau and other protein aggregates that compromise test accuracy. In AD research, there has been a growing need for Aβ imaging by two-photon microscopy, which enables deep-brain-fluorescence imaging. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00211DOI Listing

Interaction between Polysialic acid and MARCKS-ED peptide at the molecular level.

ACS Chem Neurosci 2020 May 15. Epub 2020 May 15.

Polysialic acid (polySia) is a highly negatively-charged linear homopolymer comprising α-2,8-linked sialic acids. It is abundant in the embryonic brain and modulates various functions such as differentiation and synaptic plasticity in the adult central nervous system by direct binding to its protein partners. One such example is the binding of polySia to myristoylated-alanine rich C-kinase substrate (MARCKS) to modulate neuritogenesis. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00139DOI Listing

Alzheimer's Disease "Non-amyloidogenic" p3 Peptide Revisited: A Case for Amyloid-α.

ACS Chem Neurosci 2020 Jun 22;11(11):1539-1544. Epub 2020 May 22.

Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California 95064, United States.

Amyloid-β (Aβ) is an intrinsically disordered peptide thought to play an important role in Alzheimer's disease (AD). It has been the target of most AD therapeutic efforts, which have repeatedly failed in clinical trials. A more predominant peptidic fragment, formed through alternative processing of the amyloid precursor protein, is the p3 peptide. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00160DOI Listing

Investigation of Early Death-Induced Changes in Rat Brain by Solid Phase Microextraction via Untargeted High Resolution Mass Spectrometry: versus Postmortem Comparative Study.

ACS Chem Neurosci 2020 May 29. Epub 2020 May 29.

Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, Ontario N2L 3G1, Canada.

Analysis of brain samples obtained postmortem remains a standard approach in neuroscience, despite often being suboptimal for inferring roles of small molecules in the pathophysiology of brain diseases. Sample collection and preservation further hinders conclusive interpretation of biomarker analysis in autopsy samples. We investigate purely death-induced changes affecting rat hippocampus in the first hour of postmortem interval (PMI) by means of untargeted liquid chromatography-mass spectrometry-based metabolomics. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00270DOI Listing

A Novel Tool to Investigate the Early and Late Stages of α-Synuclein Aggregation.

ACS Chem Neurosci 2020 Jun 14;11(11):1610-1619. Epub 2020 May 14.

Structural Biology and Bioinformatics Division, Indian Institute of Chemical Biology (CSIR-IICB), 4 Raja S. C. Mullick Road, Kolkata 700032, India.

The accumulation of an inherently disordered protein α-synuclein (α-syn) aggregates in brain tissue play a pivotal role in the pathology and etiology of Parkinson's disease. Aggregation of α-syn has been found to be complex and heterogeneous, occurring through multitudes of early- and late-stage intermediates. Because of the inherent complexity and large dynamic range (between a few microseconds to several days under in vitro measurement conditions), it is difficult for the conventional biophysical and biochemical techniques to sample the entire time window of α-syn aggregation. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00068DOI Listing

Therapeutic Potential of Phosphodiesterase Inhibitors against Neurodegeneration: The Perspective of the Medicinal Chemist.

ACS Chem Neurosci 2020 May 28. Epub 2020 May 28.

Department of Molecular and Translational Medicine, University of Brescia, Viale Europa 11, 25123 Brescia, Italy.

Increasing human life expectancy prompts the development of novel remedies for cognitive decline: 44 million people worldwide are affected by dementia, and this number is predicted to triple by 2050. Acetylcholinesterase and -methyl-d-aspartate receptors represent the targets of currently available drugs for Alzheimer's disease, which are characterized by limited efficacy. Thus, the search for therapeutic agents with alternative or combined mechanisms of action is wide open. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00244DOI Listing

Overexpression of Astrocytes-Specific GJA1-20k Enhances the Viability and Recovery of the Neurons in a Rat Model of Traumatic Brain Injury.

ACS Chem Neurosci 2020 Jun 13;11(11):1643-1650. Epub 2020 May 13.

Department of Neurosurgery, the People's Hospital of Shanghai Pudong New Area Affiliated to Shanghai University of Medicine and Health Sciences, Shanghai 201299, P. R. China.

Traumatic brain injury (TBI) is a devastating actuality in clinics worldwide. It is estimated that approximately 10 million people among the world suffer from TBI each year, and a considerable number of patients will be temporarily or permanently disabled or even die due to this disease. Astrocytes play a very important role in the repair of brain tissue after TBI, including the formation of a neuroprotective barrier, inhibition of brain edema, and inhibition of normal nerve cell apoptosis. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00142DOI Listing

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

ACS Chem Neurosci 2020 Jun 22;11(11):1597-1609. Epub 2020 May 22.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences and Department of Pharmacology, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia.

The metabotropic glutamate receptor 2 (mGlu) 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 mGlu relative to other closely related mGlu receptors in mediating different physiological responses, which could be achieved through the utilization of subtype selective pharmacological tools. In this respect, allosteric modulators that recognize ligand-binding sites distinct from the endogenous neurotransmitter glutamate offer the promise of higher receptor-subtype selectivity. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00009DOI Listing

Nothing Ventured, Nothing Gained: Regulations Cripple Potentially Life-Saving Research of Illicit Substances.

ACS Chem Neurosci 2020 May 12;11(10):1382-1384. Epub 2020 May 12.

Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, Alabama 36849, United States.

Modern day research, in an attempt to determine the potential therapeutic and adverse effects of illicit substances, is a growing field, but one that faces many regulatory challenges. Due to the potential abuse of illicit substances such as Cannabis, 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD) and psilocybin, regulations have been conceived with the intent of preventing harm and addiction. However, these regulations have also become a major barrier for the scientific community as they suffocate attempts of the scientists to acquire illicit substances for research purposes. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00241DOI Listing

Activity of Auranofin against Multiple Genotypes of and Its Synergistic Effect with Amphotericin B .

ACS Chem Neurosci 2020 May 26. Epub 2020 May 26.

Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92093-0756, United States.

Primary amebic meningoencephalitis, caused by brain infection with a free-living ameba, , leads to extensive inflammation of the brain and death within 3-7 days after symptoms begin. Treatment of primary amebic meningoencephalitis relies on amphotericin B in combination with other drugs, but use of amphotericin B is associated with severe adverse effects. Despite a fatality rate of over 97%, economic incentive to invest in development of antiamebic drugs by the pharmaceutical industry is lacking. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00165DOI Listing

Modulators of the Inhibitory Glycine Receptor.

ACS Chem Neurosci 2020 Jun 3. Epub 2020 Jun 3.

Department of Biochemistry, German University in Cairo, New Cairo 11835, Egypt.

The inhibitory glycine receptor is a member of the Cys-loop superfamily of ligand-gated ion channels. It is the principal mediator of rapid synaptic inhibition in the spinal cord and brainstem and plays an important role in the modulation of higher brain functions including vision, hearing, and pain signaling. Glycine receptor function is controlled by only a few agonists, while the number of antagonists and positive or biphasic modulators is steadily increasing. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00054DOI Listing

Synthetic Studies of Neoclerodane Diterpenes from Salvia divinorum: Design, Synthesis, and Evaluation of Analogues with Improved Potency and G-protein Activation Bias at the μ Opioid Receptor.

ACS Chem Neurosci 2020 May 8. Epub 2020 May 8.

Previous structure-activity relationship (SAR) studies identified the first centrally-acting, non-nitrogenous μ opioid receptor (MOR) agonist, kurkinorin (1), derived from salvinorin A. In an effort to further probe the physiological effects induced upon activation of MORs with this non-morphine scaffold, a variety of analogues were synthesized and evaluated in vitro for their ability to activate G-proteins and recruit β-arrestin-2 upon MOR activation. Through these studies, compounds that are potent agonists at MORs and either biased towards β-arrestin-2 recruitment or biased towards G-protein activation have been identified. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00191DOI Listing

α-Synuclein Regulates Iron Homeostasis via Preventing Parkin-Mediated DMT1 Ubiquitylation in Parkinson's Disease Models.

ACS Chem Neurosci 2020 Jun 20;11(11):1682-1691. Epub 2020 May 20.

Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Medical College, Qingdao University, Qingdao 266071, China.

Iron metabolism imbalance plays a key role in the neurodegeneration of Parkinson's disease (PD), thus iron homeostasis should be tightly controlled by iron transporters. α-Synuclein (α-Syn) serves as a ferrireductase and iron-binding protein, which is supposed to be linked with iron metabolism, but little is known about how α-Syn affects iron homeostasis in PD. Our previous findings that up-regulation of divalent metal transporter 1 (DMT1) accounted for the nigral iron accumulation in PD raised the question whether α-Syn disturbed iron homeostasis by modulating DMT1 expression. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00196DOI Listing
June 2020
4.362 Impact Factor

Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age.

ACS Chem Neurosci 2020 06 19;11(11):1555-1562. Epub 2020 May 19.

Department of Molecular Cell Genetics, L. Rydygier Collegium Medicum, Nicolaus Copernicus University, uI. Curie Sklodowskiej 9, 85-94 Bydgoszcz, Poland.

The COVID-19 pandemic revealed that there is a loss of smell in many patients, including in infected but otherwise asymptomatic individuals. The underlying mechanisms for the olfactory symptoms are unclear. Using a mouse model, we determined whether cells in the olfactory epithelium express the obligatory receptors for entry of the SARS-CoV-2 virus by using RNAseq, RT-PCR, in situ hybridization, Western blot, and immunocytochemistry. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241737PMC

Novel α-Lipoic Acid/3--Butylphthalide Conjugate Enhances Protective Effects against Oxidative Stress and 6-OHDA Induced Neuronal Damage.

ACS Chem Neurosci 2020 Jun 19;11(11):1634-1642. Epub 2020 May 19.

Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

Neurodegenerative diseases are irreversible conditions that result in progressive degeneration and death of nerve cells. Although the underlying mechanisms may vary, oxidative stress is considered to be one of the major causes of neuronal loss. Importantly, there are still no comprehensive treatments to completely cure these diseases. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00105DOI Listing

Astragalin Exerted Antidepressant-like Action through SIRT1 Signaling Modulated NLRP3 Inflammasome Deactivation.

ACS Chem Neurosci 2020 May 4;11(10):1495-1503. Epub 2020 May 4.

College of Pharmacy, Ningxia Medical University, Ningxia 750004, China.

Inflammation plays a key role in the pathogenesis of depression and antidepressant therapies. Astragalin (AST) is a bioactive flavonoid that possesses an anti-inflammatory property. However, the antidepressant action of astragalin has not been addressed. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00156DOI Listing

The M4 Helix Is Involved in α7 nACh Receptor Function.

ACS Chem Neurosci 2020 May 4;11(10):1406-1412. Epub 2020 May 4.

Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB 1QW, United Kingdom.

Nicotinic acetylcholine receptors (nAChR) are the archetypal members of the pentameric ligand-gated ion channel (pLGIC) family, an important class of cell signaling proteins. In all members of this family, each of the five subunits has four transmembrane α-helices (M1-M4) with M2 lining the pore and then M1 and M3, with M4 outermost and adjacent to the membrane lipids. M4 has a variety of roles: its interaction with neighboring M1 and M3 helices is important for receptor assembly, it can a transmit information on the lipid content of the membrane to the gating mechanism, and it may form a vital link to the extracellular domain via the Cys-loop. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00027DOI Listing

Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats.

ACS Chem Neurosci 2020 Jun 14;11(11):1563-1572. Epub 2020 May 14.

Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, Shandong, China.

Essential hypertension is a major risk factor for cardiovascular disease that can lead eventually to structural and functional alterations in the brain. Accumulating evidence has suggested that the increased activities in renin-angiotensin system and sympathetic nerve participated in the pathogenesis of hypertension that is related to the imbalance between neurotransmitters. The potential role in essential hypertension arising from alterations of neurotransmitters in the central nervous system remains understudied. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00699DOI Listing
June 2020
4.362 Impact Factor

Positron Emission Tomography Imaging Evaluation of a Novel F-Labeled Sigma-1 Receptor Radioligand in Cynomolgus Monkeys.

ACS Chem Neurosci 2020 Jun 20;11(11):1673-1681. Epub 2020 May 20.

Yale PET Center, Department of Radiology and Biomedical Imaging, Yale University School of Medicine, New Haven, Connecticut 06520, United States.

We report a convenient radiosynthesis and the first positron emission tomography (PET) imaging evaluation of [F]FBFP as a potent sigma-1 (σ) receptor radioligand with advantageous characteristics. [F]FBFP was synthesized in one step from an iodonium ylide precursor. In cynomolgus monkeys, [F]FBFP displayed high brain uptake and suitable tissue kinetics for quantitative analysis. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00171DOI Listing

A Master Regulator of α-Synuclein Aggregation.

Authors:
Timir Tripathi

ACS Chem Neurosci 2020 May 1;11(10):1376-1378. Epub 2020 May 1.

Molecular and Structural Biophysics Laboratory, Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India.

Parkinson's disease is associated with aggregation of pathological α-synuclein (αSyn) proteins. The central hydrophobic region of αSyn, called NAC, encodes the segment that is crucial and sufficient for the toxic aggregation of αSyn. However, if any other region, including the NAC flanking region, modulates αSyn, aggregation is still unknown. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00216DOI Listing

Investigation of the Optical Isomers of Methcathinone, and Two Achiral Analogs, at Monoamine Transporters and in Intracranial Self-Stimulation Studies in Rats.

ACS Chem Neurosci 2020 May 27. Epub 2020 May 27.

Methcathinone (MCAT; ), the progenitor of numerous and widely abused "synthetic cathinone" central stimulants, exists as a pair of optical isomers. Although (-)MCAT is several-fold more potent than (+)MCAT in rodent locomotor stimulation and in stimulus generalization studies in rat drug discrimination assays, the individual optical isomers of MCAT have never been directly compared for their actions at monoamine transporters that seem to underlie their actions and have never been examined for their relative abuse potential. Here, we found that the isomers of MCAT are nearly equieffective at dopamine and norepinephrine transporters (DAT and NET, respectively) as transporter substrates (. Read More

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http://dx.doi.org/10.1021/acschemneuro.9b00617DOI Listing
May 2020
4.362 Impact Factor

GLUT-1: An Effective Target To Deliver Brain-Derived Neurotrophic Factor Gene Across the Blood Brain Barrier.

ACS Chem Neurosci 2020 Jun 12;11(11):1620-1633. Epub 2020 May 12.

Department of Pharmaceutical Sciences, School of Pharmacy, College of Health Professions, North Dakota State University, Fargo, North Dakota 58105, United States.

Alzheimer's disease (AD), the most common cause of dementia, inflicts enormous suffering to patients and their family members. It is the third deadliest disease, affecting 46.8 million people worldwide. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00076DOI Listing
June 2020
4.362 Impact Factor

LncRNA GAS5 and miR-137 Polymorphisms and Expression are Associated with Multiple Sclerosis Risk: Mechanistic Insights and Potential Clinical Impact.

ACS Chem Neurosci 2020 Jun 12;11(11):1651-1660. Epub 2020 May 12.

Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.

The pathogenesis of multiple sclerosis (MS) is influenced by the interaction of genetic and epigenetic mechanisms. The long noncoding RNA GAS5 acts as a competing endogenous RNA for microRNA-137 and is involved in demyelination. We investigated the association of GAS5 and miR-137 expression and their polymorphisms with MS susceptibility. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00150DOI Listing
June 2020
4.362 Impact Factor

Is the Collapse of the Respiratory Center in the Brain Responsible for Respiratory Breakdown in COVID-19 Patients?

ACS Chem Neurosci 2020 05 29;11(10):1379-1381. Epub 2020 Apr 29.

CSIR-Indian Institute of Chemical Biology (CSIR-IICB), Kolkata 700032, India.

Following the identification of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, we are now again facing a global highly pathogenic novel coronavirus (SARS-CoV-2) epidemic. Although the lungs are one of the most critically affected organs, several other organs, including the brain may also get infected. Here, we have highlighted that SARS-CoV-2 might infect the central nervous system (CNS) through the olfactory bulb. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192347PMC

Migraine and Ischemic Stroke: Deciphering the Bidirectional Pathway.

ACS Chem Neurosci 2020 Jun 12;11(11):1525-1538. Epub 2020 May 12.

Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Ahmedabad, Gandhinagar, Gujarat 382355, India.

Migraine and stroke are common, disabling neurological conditions with several theories being proposed to explain this bidirectional relationship. Migraine is considered as a benign neurological disorder, but research has revealed a connection between migraine and stroke, predominantly those having migraine with aura (MA). Among migraineurs, females with MA are more susceptible to ischemic stroke and may have a migrainous infarction. Read More

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http://dx.doi.org/10.1021/acschemneuro.0c00137DOI Listing