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ACS Chemical Neuroscience

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https://www.readbyqxmd.com/read/30396272/synthesis-and-in-vivo-evaluation-of-a-novel-pet-radiotracer-for-imaging-of-synaptic-vesicle-glycoprotein-2a-sv2a-in-non-human-primates
#1
Songye Li, Zhengxin Cai, Xiaoai Wu, Daniel Holden, Richard Pracitto, Michael Kapinos, Hong Gao, David C Labaree, Nabeel Nabulsi, Richard E Carson, Yiyun Huang
Structural disruption and alterations of synapses are associated with many brain disorders, including Alzheimer's disease, epilepsy, depression and schizophrenia. We have previously developed the PET radiotracer 11 C-UCB-J for imaging and quantification of synaptic vesicle glycoprotein 2A (SV2A) and synaptic density in non-human primates and humans. Here we report the synthesis of a novel radiotracer 18 F-SDM-8 and its in vivo evaluation in rhesus monkeys. The in vitro binding assay of SDM-8 showed high SV2A binding affinity ( Ki = 0...
November 6, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30396268/genetic-and-pharmacological-targeting-of-heat-shock-protein-70-in-the-mouse-amygdala-kindling-model
#2
Eva-Lotta von Rüden, Fabio Wolf, Fabio Gualtieri, Michael Keck, Clayton R Hunt, Tej K Pandita, Heidrun Potschka
Inflammatory responses involving Toll-like receptor signaling represent a key factor contributing to epileptogenesis. Thus, it is of particular interest to explore the relevance of toll-like receptor ligands and modulators, such as heat shock protein 70 (HSP70). Motivated by recent findings demonstrating an upregulation of HSP70 in a model of epileptogenesis, we analyzed the consequences of genetic and pharmacological targeting of HSP70 expression in a mouse kindling paradigm. Lack of inducible HSP70 resulted in increased prekindling seizure thresholds...
November 16, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30399321/stimulations-of-the-culture-medium-of-activated-microglia-and-tnf-alpha-on-a-scrapie-infected-cell-line-decrease-the-cell-viability-and-induce-marked-necroptosis-that-also-occurs-in-the-brains-from-the-patients-of-human-prion-diseases
#3
Yue Ma, Qi Shi, Kang Xiao, Jing Wang, Cao Chen, Li-Ping Gao, Chen Gao, Xiao-Ping Dong
Activation of microglia and increased expression of TNF-α are frequently observed in the brains of human and animal prion diseases. As an important cytokine, TNF-α participates in not only pro-inflammatory responses but also in cellular communication, cell differentiation, and cell death. However, the role of TNF-α in the pathogenesis of prion disease remains ambiguous. In this study, the activities of a scrapie-infected cell line SMB-S15 and its normal partner SMB-PS exposed to the supernatant of a LPS-activated microglia cell line BV2 were evaluated...
November 15, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30428260/an-engineered-variant-of-the-b1-domain-of-protein-g-suppresses-the-aggregation-and-toxicity-of-intra-and-extracellular-a%C3%AE-42
#4
Victor Banerjee, Ofek Oren, Bar Dagan, Ran Taube, Stanislav Engel, Niv Papo
Intra- and extra-neuronal deposition of amyloid β (Aβ) peptides have been linked to Alzheimer's disease (AD). While both intra- and extraneuronal Aβ deposits affect neuronal cell viability, the molecular mechanism by which these Aβ structures, especially when intraneuronal, do so is still not entirely understood. This makes the development of inhibitors challenging. To prevent the formation of toxic Aβ structural assemblies so as to prevent neuronal cell death associated with AD, we used a combination of computational and combinatorial-directed evolution approaches to develop a variant of the HTB1 protein (HTB1M2)...
November 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30427662/neuro-regenerative-choline-functionalized-injectable-graphene-oxide-hydrogel-repairs-focal-brain-injury
#5
Krishnangsu Pradhan, Gaurav Das, Juhee Khan, Varsha Gupta, Surajit Barman, Anindyasundar Adak, Surajit Ghosh
Brain damage is associated with spatial imbalance of cholinergic system, which makes severe impact in recovery of damaged neurons of brain. Therefore, maintenance of cholinergic system is extremely important. Here, we fabricated an injectable hydrogel with acetylcholine functionalized graphene oxide and polyacrylic acid. Results revealed that this hydrogel is non-cytotoxic, promotes neurite outgrowth, stabilizes microtubule networks, and enhances the expression of some key neural markers in rat cortical primary neurons...
November 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30403473/dark-classics-in-chemical-neuroscience-opium-a-friend-or-foe
#6
Parvez Alam, Subhomoi Borkokoty, Mohammad Khursheed Siddiqi, Aquib Ehtram, Nabeela Majid, Moin Uddin, Rizwan Hasan Khan
Opium has found great use medicinally for its analgesic properties and has been witnessed as one of the most popular medications used in psychiatry. Opium derivatives have been shown as efficacious for relieving pain and the treatment of epileptic seizures, but progressive research toward their use in the treatment of neurodegenerative diseases remain elusive. To gain more insight into the other properties of opium such as anti-inflammatory properties, herein we discuss basic information regarding opium, opium content and mechanism of action, pharmacology of opium derivatives, the role of opium in the prevention of neurodegeneration, and adverse effects of opium derivatives on neuronal health...
November 14, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30421909/neuroprotective-efficacy-of-a-novel-sigma-2-receptor-tmem97-modulator-dkr-1677-after-traumatic-brain-injury
#7
Edwin Vázquez-Rosa, Michael R Watson, James J Sahn, Timothy Robert Hodges, Rachel E Schroeder, Coral J Cintrón-Pérez, Min-Kyoo Shin, Terry C Yin, Josie L Emery, Stephen F Martin, Daniel J Liebl, Andrew Pieper
Compounds targeting the sigma 2 receptor, which we recently cloned and showed to be identical with transmembrane protein 97 (2R/TMEM97), are broadly applicable therapeutic agents currently in clinical trials for imaging in breast cancer and for treatment of Alzheimer's disease and schizophrenia. These promising applications coupled with our previous observation that the 2R/TMEM97 modulator SAS-0132 has neuroprotective attributes and improves cognition in wild type mice, suggests that modulating 2R/TMEM97 may also have therapeutic benefits in other neurodegenerative conditions, such as traumatic brain injury (TBI)...
November 13, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30384594/c-terminal-cu-ii-coordination-to-%C3%AE-synuclein-enhances-aggregation
#8
Dinendra L Abeyawardhane, Denver R Heitger, Ricardo D Fernández, Ashley K Forney, Heather R Lucas
The structurally dynamic amyloidogenic protein α-synuclein (αS) is universally recognized as a key player in Parkinson's disease (PD). Copper, which acts as a neuronal signaling agent, is also an effector of αS structure, aggregation, and localization in vivo. In humans, αS is known to carry an acetyl group on the starting methionine residue, capping the N-terminal free amine which was a known high-affinity CuII binding site. We now report the first detailed characterization data using electron paramagnetic resonance (EPR) spectroscopy to describe the CuII coordination modes of N-terminally acetylated αS (NAc αS)...
November 13, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30418735/ethanol-and-naltrexone-have-distinct-effects-on-the-lateral-nano-organization-of-mu-and-kappa-opioid-receptors-in-the-plasma-membrane
#9
Steven J Tobin, Devin L Wakefield, Lars Terenius, Vladana Vukojević, Tijana Jovanović-Talisman
The complex spatiotemporal organization of proteins and lipids in the plasma membrane is an important determinant of receptor function. Certain substances, such as ethanol, can penetrate into the hydrophobic regions of the plasma membrane. By altering protein-lipid and protein-protein interactions, these substances can modify the dynamic lateral organization and the function of plasma membrane receptors. To assess changes in plasma membrane receptor organization, we used photoactivated localization microscopy (PALM)...
November 12, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30412668/pathological-impacts-of-chronic-hypoxia-on-alzheimer-s-disease
#10
Feng Zhang, Long Niu, Song Li, Weidong Le
Chronic hypoxia is considered as one of the important environmental factors contributing to the pathogenesis of Alzheimer's disease (AD). Many chronic hypoxia-causing comorbidities, such as obstructive sleep apnea syndrome (OSAS) and chronic obstructive pulmonary disease (COPD), have been reported to be closely associated with AD. Increasing evidence has documented that chronic hypoxia may affect many pathological aspects of AD including amyloid β (Aβ) metabolism, tau phosphorylation, autophagy, neuroinflammation, oxidative stress, endoplasmic reticulum (ER) stress, mitochondrial and synaptic dysfunction, which may collectively result in neuron degeneration in the brain...
November 9, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30412381/nmda-receptor-dependent-cholinergic-modulation-of-mesolimbic-dopamine-cell-bodies-neurochemical-and-behavioral-studies
#11
Marina Spanos, Xiaohu Xie, Julie Gras-Najjar, Stephanie C White, Leslie A Sombers
Substance abuse disorders are devastating, costly, and difficult to treat. Identifying the neurochemical mechanisms underlying reinforcement promises to provide critical information in the development of effective treatments. Several lines of evidence suggest that striatal dopamine (DA) release serves as a teaching signal in reinforcement learning, and that shifts in DA release from the primary reward to reward-predicting stimuli play a critical role in the self-administration of both natural and non-natural rewards...
November 9, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30408415/discovery-of-neuro-regenerative-peptoid-from-amphibian-neuropeptide-inhibits-a%C3%AE-toxicity-and-crossed-blood-brain-barrier
#12
Krishnangsu Pradhan, Gaurav Das, Varsha Gupta, Prasenjit Mondal, Surajit Barman, Juhee Khan, Surajit Ghosh
Development of potential therapeutics for Alzheimer's disease (AD) required multifaceted strategy considering the high level of complexities of human brain and its mode of function. Here, we adopted an advanced strategy targeting two key pathological hallmarks of AD such as senile plaque and neurofibrillary tangles. We derived a lead short tetrapeptide Ser-Leu-Lys-Pro (SLKP) from dodeca-neuropeptide of amphibian (frog) brain. Results suggest that SLKP peptide has superior effect compared to the dodecapeptide in neuroprotection...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30407786/structure-based-drug-designing-recommends-hdac6-inhibitors-to-attenuate-microtubule-associated-tau-pathogenesis
#13
Amir Zeb, Chanin Park, Shailima Rampogu, Minky Son, GiHwan Lee, Keun Woo Lee
Protein acetylation and deacetylation play vital roles in the structural and physiological behavior of target proteins. Histone deacetylase 6 (HDAC6) remains a key therapeutic target in several chronic diseases such as cancer, neurodegenerative, and hematological diseases. In tau-pathogenesis, HDAC6 tightly regulates microtubule-associated tau physiology, and its inhibition suppresses Alzheimer's phenotype. To this end, the current study has identified novel HDAC6 inhibitors by structure-based drug designing method...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30406996/role-of-cse-produced-h2s-on-cerebrovascular-relaxation-via-rhoa-rock-inhibition-and-cerebral-ischemia-reperfusion-injury-in-mice
#14
Jiyue Wen, Shanshan Gao, Fanglin Chen, Shuo Chen, Mei Wang, Zhiwu Chen
Role of CSE-produced H2S on cerebrovascular relaxation and cerebral ischemia-reperfusion (I/R) injury were investigated using CSE knockout (CSE-/-) and wild-type (CSE+/+) mice. The relaxation of cerebral basilar artery (BA) to CSE-produced H2S and its mechanism were detected. The results revealed that both NaHS, donor of exogenous H2S and ROCK inhibitor Y27632 could induce significant relaxation of BA, but the relaxation of BA to NaHS was significantly attenuated by Y27632. In addition, removal of endothelium could reduce the relaxation of BA to Y27632; CSE knockout also significantly attenuated Y27632-induced BA relaxation with endothelium rather than without endothelium...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30399318/azelnidipine-attenuates-the-oxidative-and-nf%C3%AE%C2%BAb-pathways-in-amyloid-%C3%AE-stimulated-cerebral-endothelial-cells
#15
Tao Teng, Devin M Ridgley, Andrey Tsoy, Grace Y Sun, Sholpan Askarova, James C Lee
Cerebral amyloid angiopathy (CAA), a condition depicting cerebrovascular accumulation of amyloid β-peptide (Aβ), is a common pathological manifestation in Alzheimer's disease (AD). In this study, we investigated the effects of Azelnidipine (ALP), a dihydropyridine calcium channel blocker known for its treatment of hypertension, on oligomeric Aβ (oAβ)-induced calcium influx and its downstream pathway in immortalized mouse cerebral endothelial cells (bEND3). We found that ALP attenuated oAβ-induced calcium influx, superoxide anion production, and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and calcium-dependent cytosolic phospholipase A2 (cPLA2 )...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30384585/ruboxistaurin-reduces-cocaine-stimulated-increases-in-extracellular-dopamine-by-modifying-dopamine-autoreceptor-activity
#16
Alexander G Zestos, Colleen Carpenter, Youngsoo Kim, Malcolm J Low, Robert T Kennedy, Margaret E Gnegy
Cocaine is a highly abused drug, and cocaine addiction affects millions of individuals worldwide. Cocaine blocks normal uptake function at the dopamine transporter (DAT), thus increasing extracellular dopamine. Currently, no chemical therapies are available to treat cocaine abuse. Previous works showed that the selective inhibitors of protein kinase Cβ (PKCβ), enzastaurin and ruboxistaurin, attenuate dopamine overflow and locomotion stimulated by another psychostimulant drug, amphetamine. We now test if ruboxistaurin similarly affects cocaine action...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30375852/-methylene-bridge-to-5-ht-3-receptor-antagonists-conformationally-constrained-phenylguanidines
#17
Ahmed S Abdelkhalek, Genevieve S Alley, Osama I Alwassil, Shailesh Khatri, Philip D Mosier, Heather L Nyce, Michael M White, Marvin K Schulte, Małgorzata Dukat
Arylguanidines, depending upon their aromatic substitution pattern, display varying actions at 5-HT3 receptors (e.g., partial agonist, agonist, superagonist). Here, we demonstrate that conformational constraint of these agents as dihydroquinazolines (such as A6CDQ; 1) results in their conversion to 5-HT3 receptor antagonists. We examined the structure-activity relationships of 1. Replacement/removal of any of the guanidinium nitrogen atoms of 1 resulted in decreased affinity. All three nitrogen atoms of 1 are necessary for optimal binding affinity at 5-HT3 receptors...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30375847/biochemical-changes-indicate-developmental-stage-in-the-hippocampal-formation
#18
Joanna G Chwiej, Stanislaw W Ciesielka, Agnieszka K Skoczen, Krzysztof J Janeczko, Christophe Sandt, Karolina L Planeta, Zuzanna K Setkowicz
The literature showing how age of humans or animals influences the IR absorption spectra recorded in different brain regions is very poor. A very limited number of studies used FTIR microspectroscopy for analysis of the aging process, however there is lack of data concerning the biomolecular changes occurring in the course of postnatal development of the central nervous system. Therefore, in this paper the topographic and semiquantitative biochemical changes occurring within the rat hippocampus during postnatal development were examined...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30372021/classics-in-chemical-neuroscience-donepezil
#19
James T Brewster, Simone Dell'Acqua, Danny Q Thach, Jonathan L Sessler
The discovery of acetylcholine and acetylcholinesterase provided the first insight into the intricacies of chemical signal transduction and neuronal communication. Further elucidation of the underlying mechanisms led to an attendant leveraging of this knowledge via the synthesis of new therapeutics designed to control aberrant biochemical processes. The central role of the cholinergic system within human memory and learning, as well as its implication in Alzheimer's disease, has made it a point of focus within the neuropharmacology and medicinal chemistry communities...
November 8, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/30362702/molecular-mechanisms-of-neurotoxicity-induced-by-polymyxins-and-chemoprevention
#20
Chongshan Dai, Xilong Xiao, Jichang Li, Giuseppe D Ciccotosto, Roberto Cappai, Shusheng Tang, Elena K Schneider-Futschik, Daniel Hoyer, Tony Velkov, Jianzhong Shen
Neurotoxicity is one major unwanted side-effects associated with polymyxin (i.e., colistin and polymyxin B) therapy. Clinically, colistin neurotoxicity is characterized by neurological symptoms including dizziness, visual disturbances, vertigo, confusion, hallucinations, seizures, ataxia, and facial and peripheral paresthesias. Pathologically, colistin-induced neurotoxicity is characterized by cell injury and death in neuronal cell. This Review covers our current understanding of polymyxin-induced neurotoxicity, its underlying mechanisms, and the discovery of novel neuroprotective agents to limit this neurotoxicity...
November 7, 2018: ACS Chemical Neuroscience
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