Abstract:
: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.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Prevot TD,Li G,Cook JM,Sibille Edoi
10.1021/acschemneuro.9b00148subject
Has Abstractpub_date
2019-05-15 00:00:00pages
2088-2090issue
5issn
1948-7193journal_volume
10pub_type
杂志文章abstract::The sensory nervous system controls cardiovascular homeostasis via capsaicin-sensitive neurons that release calcitonin gene-related peptide (CGRP), which subsequently activates CGRP receptors. How this perivascular CGRPergic discharge is modulated, nevertheless, remains unclear. In pithed rats, systemic vasodilation i...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00277
更新日期:2019-08-21 00:00:00
abstract::Neuroinflammatory processes promote a constellation of neurochemical and hormonal changes resulting in profound effects on motivational states (anhedonia), mood (depression and anxiety disorders), and cognitive function (decrements in learning and memory). The enhancement of immunoregulatory processes, such as increas...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00386
更新日期:2019-01-16 00:00:00
abstract::Human epidemiological and animal-model studies suggest that separate exposure to stress or serotonin-selective reuptake inhibitor (SSRI) antidepressants during pregnancy increases risks for neurodevelopmental disorders in offspring. Yet, little is known about the combined effects of maternal stress and SSRIs with rega...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
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abstract::Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inh...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00023
更新日期:2018-01-17 00:00:00
abstract::The l-enantiomer is the predominant type of amino acid in all living systems. However, d-amino acids, once thought to be "unnatural", have been found to be indigenous even in mammalian systems and increasingly appear to be functioning in essential biological and neurological roles. Both d- and l-amino acid levels in t...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00398
更新日期:2017-06-21 00:00:00
abstract::Krokodil is the street name for a homemade mixture that has been used as a cheap substitute for heroin. The main active substance in krokodil is desomorphine, an opioid that is 10 times more potent than morphine. Krokodil use began in Russia and Ukraine but has spread throughout several countries in Europe and North A...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00495
更新日期:2020-09-17 00:00:00
abstract::Oxidative stress is a hallmark of several aging and trauma related neurological disorders, but the precise details of how altered neuronal activity elicits subcellular redox changes have remained difficult to resolve. Current redox sensitive dyes and fluorescent proteins can quantify spatially distinct changes in reac...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00342
更新日期:2020-09-02 00:00:00
abstract::Opium is the latex from the opium poppy Papaver somniferum L., which humankind has utilized since ancient Mesopotamia all the way to modern times. Opium used to be surrounded in divine mystery or magic-like abilities and was given to cure a wide variety of diseases until its analgesic, antitussive, and antidiarrheal p...
journal_title:ACS chemical neuroscience
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acschemneuro.8b00459
更新日期:2018-10-17 00:00:00
abstract::Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and their effects on SOD1 aggregation remain unclear. This paper...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00086
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journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00632
更新日期:2019-01-16 00:00:00
abstract::MMP-9 plays a detrimental role in the pathology of several neurological diseases and, thus, represents an important target for intervention. The water-soluble prodrug ND-478 is hydrolyzed to the active MMP-9 inhibitor ND-322, which in turn is N-acetylated to the even more potent metabolite ND-364. We used a sensitive ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn400077d
更新日期:2013-08-21 00:00:00
abstract::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 t...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.9b00699
更新日期:2020-06-03 00:00:00
abstract::Tau proteins are hyperphosphorylated at common sites in their N- and C-terminal domains in at least three neurodegenerative diseases, Parkinson, dementia with Lewy bodies, and Alzheimer's, suggesting specific pathology but general mechanism. Full-length human tau filament comprises a rigid core and a two-layered fuzzy...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00294
更新日期:2016-05-18 00:00:00
abstract::Several pharmacophore models have been proposed for 5-HT2A serotonin receptor antagonists. These typically consist of two aromatic/hydrophobic moieties separated by a given distance from each other, and from a basic amine. Although specified distances might vary, the models are relatively similar in their general cons...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00162
更新日期:2016-09-21 00:00:00
abstract::CBD-2115 was selected from a library of 148 compounds based on a pyridinyl-indole scaffold as a first-in-class 4R-tau radiotracer. In vitro binding assays showed [3H]CBD-2115 had a KD value of 6.9 nM and a nominal Bmax of 500 nM in 4R-tau expressing P301L transgenic mouse tissue. In binding assays with human brain tis...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00801
更新日期:2021-01-26 00:00:00
abstract::We propose a tripartite mechanism to describe the processing of cognitive information (cog-info), comprising the (1) neuron, (2) surrounding neural extracellular matrix (nECM), and (3) numerous "trace" metals distributed therein. The neuron is encased in a polyanionic nECM lattice doped with metals (>10), wherein it p...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/cn300237r
更新日期:2013-06-19 00:00:00
abstract::Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) autophosphorylation at Thr286 and Thr305/Thr306 regulates kinase activity and modulates subcellular targeting and is critical for normal synaptic plasticity and learning and memory. Here, a mass spectrometry-based approach was used to identify Ca(2+)-dependent a...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn500337u
更新日期:2015-04-15 00:00:00
abstract::A new generation of ligands designed to interact with the α-helix/β-strand discordant region of the amyloid-β peptide (Aβ) and to counteract its oligomerization is presented. These ligands are designed to interact with and stabilize the Aβ central helix (residues 13-26) in an α-helical conformation with increased inte...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00485
更新日期:2019-03-20 00:00:00
abstract::The glycine receptor (GlyR) is a ligand-activated chloride channel, whose mutations are the major cause of hereditary hyperekplexia. The hyperekplexia-causing R271Q mutation, which is located at the extracellular outer mouth of the channel pore, dramatically impairs the GlyR function manifesting a reduced sensitivity ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00522
更新日期:2020-10-21 00:00:00
abstract::Botulinum neurotoxin (BoNT), the etiological agent that causes the neuroparalytic disease botulism, has become a highly studied drug target in light of the potential abuse of this toxin as a weapon of bioterrorism. In particular, small molecule inhibitors of the light chain metalloprotease of BoNT serotype A have rece...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn200021q
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abstract::Neurons choose growth pathways with half hearted reluctance, behavior that may be appropriate to maintain fixed long lasting connections but not to regenerate them. We now recognize that intrinsic brakes on regrowth are widely expressed in these hesitant neurons and include classical tumor suppressor molecules. Here, ...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
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abstract::Amyloid-β (Aβ) is a peptide fragment that is prone to aggregate into large fibrils under physiological conditions. Many techniques have been developed to quickly monitor the transition from a primarily monomeric peptide into fibrils. Here we propose a novel method for both incubating and monitoring changes in Aβ aggre...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/cn300135n
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abstract::Altered intestinal permeability has been correlated with Parkinson's pathophysiology in the enteric nervous system, before manifestations in the central nervous system (CNS). The inflammatory endotoxin or lipopolysaccharide (LPS) released by gut bacteria is known to modulate α-synuclein amyloidogenesis through the for...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.8b00733
更新日期:2019-05-15 00:00:00
abstract::Small hydrophobic oligomers of aggregation-prone proteins are thought to be generically toxic. Here we examine this view by perturbing an early folding contact between Phe19 and Leu34 formed during the aggregation of Alzheimer's amyloid-β (Aβ40) peptide. We find that even conservative single mutations altering this in...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.5b00074
更新日期:2015-08-19 00:00:00
abstract::No selective drugs exist, and we have been designing, synthesizing, and evaluating multitarget-directed ligands since the beginning of modern medicinal chemistry, without knowing it, most possibly. The challenge to discover the efficient Multi-Target Small Molecules (MTSMs) for Alzheimer's disease (AD) therapy implies...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章,评审
doi:10.1021/acschemneuro.8b00069
更新日期:2018-03-21 00:00:00
abstract::Accumulating evidence suggested that soluble oligomeric β-amyloid protein (Aβ) exerts diverse roles in neuronal cell death, neuroinflammation, oxidative stress, and the eventual dementia associated with Alzheimer's disease (AD). Developing an agent with multiple properties may be a reasonable strategy for the treatmen...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.6b00091
更新日期:2016-04-20 00:00:00
abstract::The discovery of haloperidol catalyzed a breakthrough in our understanding of the biochemical basis of schizophrenia, improved the treatment of psychosis, and facilitated deinstitutionalization. In doing so, it solidified the role for chemical neuroscience as a means to elucidate the molecular underpinnings of complex...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00018
更新日期:2017-03-15 00:00:00
abstract::Sevoflurane, one of the most commonly used anesthetic agents, has been demonstrated to induce widespread neurodegeneration in the developing brain. We aimed to evaluate the protective effects of a PDE-7 inhibitor (BRL-50481) against the neurotoxic effects of sevoflurane on the developing nervous system. Spatial learni...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.0c00106
更新日期:2020-05-06 00:00:00
abstract::The antioxidant activity of selenium, which is mainly conferred by its incorporation into dedicated selenoproteins, has been suggested as a possible neuroprotective approach for mitigating neuronal loss in Alzheimer's disease. However, there is inconsistent information with respect to selenium levels in the Alzheimer'...
journal_title:ACS chemical neuroscience
pub_type: 杂志文章
doi:10.1021/acschemneuro.7b00014
更新日期:2017-07-19 00:00:00
abstract::Aminorex (5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) and 4-methylaminorex (4-methyl-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine) are psychostimulants that have long been listed in Schedules IV and I of the UN Convention on Psychotropic Substances of 1971. However, a range of psychoactive analogues exist that are not interna...
journal_title:ACS chemical neuroscience
pub_type: 历史文章,杂志文章,评审
doi:10.1021/acschemneuro.8b00415
更新日期:2018-10-17 00:00:00