Abstract：
:Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-β aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-β aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-β plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-β imaging agents for early stage Alzheimer's.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Neo Shin N,Jeon H,Jung Y,Baek S,Lee S,Yoo HC,Bae GH,Park K,Yang SH,Han JM,Kim I,Kim Ydoi
10.1021/acschemneuro.9b00093subject
Has Abstractpub_date
2019-06-19 00:00:00pages
3031-3044issue
6issn
1948-7193journal_volume
10pub_type
杂志文章abstract：:Depression, a major cause of disability worldwide, is characterized by a complex and heterogeneous symptomatology. With this respect, cognitive deterioration represents a major problem that has a strong impact on a patient's function. Thus, within the context of a depressive phenotype, it is important to characterize ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00392
更新日期：2017-04-19 00:00:00
abstract：:Serotonin (5-HT) is a key player in many physiological processes in both the adult organism and developing embryo. One of the mechanisms for 5-HT-mediated effects is covalent binding of 5-HT to the target proteins catalyzed by transglutaminases (serotonylation). Despite the implication in a variety of physiological pr...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00346
更新日期：2019-08-21 00:00:00
abstract：:We have previously designed and synthesized a series of novel memantine nitrates, and some of them have shown neuroprotective effects; however, the detailed mechanisms remain unknown. In this study, we demonstrated that MN-12, one of the memantine nitrates, concentration-dependently protected against glutamate-induced...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00242
更新日期：2020-02-05 00:00:00
abstract：:The aggregation of α-synuclein (α-Syn) has been implicated strongly in Parkinson's disease (PD). The intrinsically disordered nature of α-Syn makes this protein prone to self-association or heteroassociation with another protein or lipid. While conformational fluctuation and free radical chemistry have been shown to p...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00393
更新日期：2019-03-20 00:00:00
abstract：:Early diagnosis in Alzheimer's disease (AD), prior to the appearance of marked clinical symptoms, is critical to prevent irreversible neuronal damage and neural malfunction that lead to dementia and death. Therefore, there is an urgent need to generate new contrast agents which reveal by a noninvasive method the prese...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00260
更新日期：2018-05-16 00:00:00
abstract：:Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100012x
更新日期：2010-05-19 00:00:00
abstract：:The molecular pathogenesis of Alzheimer's disease (AD) is complex and sparsely understood. The relationship between AD's amyloid β (Aβ) peptides and neuronal membranes is central to Aβ's cytotoxicity and is directly modulated by the composition of the lipid headgroups. Molecular studies of the insertion of model Aβ40 ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500277f
更新日期：2015-03-18 00:00:00
abstract：:Relapse to cocaine dependence, even after extended abstinence, involves a number of liability factors including impulsivity (predisposition toward rapid, unplanned reactions to stimuli without regard to negative consequences) and cue reactivity (sensitivity to cues associated with cocaine-taking which can promote coca...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300072u
更新日期：2013-01-16 00:00:00
abstract：:Intra- and extraneuronal 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 ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00491
更新日期：2019-03-20 00:00:00
abstract：:Alzheimer's disease (AD) is the most common form of dementia affecting 35 million individuals worldwide. Current AD treatments provide only brief symptomatic relief. It is therefore urgent to replace this symptomatic approach with a curative one. Increasing serotonin signaling as well as developing molecules that enha...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00135
更新日期：2015-07-15 00:00:00
abstract：:NLRP3-PYD inflammasome activates an inflammatory pathway in response to a wide variety of cell damage or infections. Dysregulated NLRP3 inflammatory signaling has many chronic inflammatory and autoimmune disorders. NLRP3 and ASC have a PYD, a superfamily member of the Death Domain, which plays a key role in inflammato...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00519
更新日期：2021-01-27 00:00:00
abstract：:Natural environments contain numerous volatile compounds emanating from a large number of sources, and the survival of many animals depends on their ability to segregate odors of interest within complex odorous scenes. In a recent paper, we described how the ability of mice to detect odors within mixtures depends on t...
journal_title：ACS chemical neuroscience
pub_type： 评论,杂志文章
doi：10.1021/cn500199n
更新日期：2014-10-15 00:00:00
abstract：:Tropomyosin receptor kinases (TrkA/B/C) are critically involved in the development of the nervous system, in neurological disorders as well as in multiple neoplasms of both neural and non-neural origins. The development of Trk radiopharmaceuticals would offer unique opportunities toward a more complete understanding o...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500193f
更新日期：2015-02-18 00:00:00
abstract：:Azobenzenes are the most widely studied photoswitches, and have become popular optical probes for biological systems. The cis configuration is normally metastable, meaning the trans configuration is always thermodynamically favored. The unique exception to this rule is an azobenzene having a two-carbon bridge between ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00734
更新日期：2019-05-15 00:00:00
abstract：:Glutamate is the major excitatory transmitter in the mammalian CNS, exerting its effects through both ionotropic and metabotropic glutamate receptors. The metabotropic glutamate receptors (mGlus) belong to family C of the G-protein-coupled receptors (GPCRs). The eight mGlus identified to date are classified into three...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100099n
更新日期：2011-08-17 00:00:00
abstract：:SARS-CoV-2 remains a significant burden on human health. Several lines of evidence suggest that surveillance of sewage and waste can provide an early warning sign for COVID-19 recurrence in a community. In support, SARS-CoV-2 traces were found in sewage in several countries. With this in mind, it is notable that pests...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.0c00312
更新日期：2020-07-01 00:00:00
abstract：:The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, w...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100093f
更新日期：2011-02-16 00:00:00
abstract：:Oligomers of amyloid-β (AβO) are deemed key in synaptotoxicity and amyloid seeding of Alzheimer's disease (AD). However, the heterogeneous and dynamic nature of AβO and inadequate markers for AβO subtypes have stymied effective AβO identification and therapeutic targeting in vivo. We identified an AβO-subclass epitope...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00469
更新日期：2018-07-18 00:00:00
abstract：:The present study was performed to investigate the possible role of protein kinase C (PKC) in morphine tolerance at spinal levels of rats. Intrathecal injection of 10 μg of morphine induced increases in the hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation in rats. After intrathecal inject...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn900005d
更新日期：2010-02-17 00:00:00
abstract：:Metabolic adaptation to stress is a crucial yet poorly understood phenomenon, particularly in the central nervous system (CNS). The ability to identify essential metabolic events which predict neuronal fate in response to injury is critical to developing predictive markers of outcome, for interpreting CNS spectroscopi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300003r
更新日期：2012-07-18 00:00:00
abstract：:Alzheimer's disease is a progressive neurodegenerative disorder that mainly affects the elderly. Soluble β-amyloid oligomer, which can induce neurotoxicity, is generally regarded as the main neurotoxin in Alzheimer's disease. Here we report that eckmaxol, a phlorotannin extracted from the brown alga Ecklonia maxima, c...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00527
更新日期：2018-06-20 00:00:00
abstract：:High levels of histamine H3 receptors (H3Rs) are found in the globus pallidus (GP), a neuronal nucleus in the basal ganglia involved in the control of motor behavior. By using rat GP isolated nerve terminals (synaptosomes), we studied whether H3R activation modified the previously reported enhancing action of adenosin...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500001m
更新日期：2014-08-20 00:00:00
abstract：:The enantiomers of the potent σ1 receptor antagonist (±)-1 were synthesized and evaluated for their affinity at σ1, σ2 receptors and dopamine transporter (DAT). Analogously to (±)-1, both of the enantiomers showed very high affinity for the σ1 receptor and unprecedented selectivity over both the σ2 receptor and DAT. T...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00261
更新日期：2019-08-21 00:00:00
abstract：:Amyloid β (Abeta) peptides in their oligomeric form have been proposed as major toxic species in Alzheimer's disease (AD). There are a limited number of anti-Abeta antibodies specific to oligomeric forms of Abeta compared to the monomeric form, and accurate measurement of oligomeric forms in biological samples, cerebr...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn3001262
更新日期：2012-11-21 00:00:00
abstract：:While selective-serotonin reuptake inhibitor (SSRI) antidepressants are commonly prescribed in the treatment of depression, their use during pregnancy leads to fetal drug exposures. According to recent reports, such exposures could affect fetal development and long-term offspring health. A central question is how preg...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00287
更新日期：2016-03-16 00:00:00
abstract：:The lower efficacy of opioids in neuropathic pain may be due to the increased activity of pronociceptive systems such as substance P. We present evidence to support this hypothesis in this work from the spinal cord in a neuropathic pain model in mice. Biochemical analysis confirmed the elevated mRNA and protein level ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00226
更新日期：2017-10-18 00:00:00
abstract：:Development of pharmacological tools for the ionotropic glutamate receptors (iGluRs) is imperative for the study and understanding of the role and function of these receptors in the central nervous system. We report the synthesis of 18 analogues of (2 S,3 R)-2-carboxy-3-pyrrolidine acetic acid (3a), which explores the...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00205
更新日期：2019-06-19 00:00:00
abstract：:We recently found that tamoxifen suppresses l-glutamate transport activity of cultured astrocytes. Here, in an attempt to separate the l-glutamate transporter-inhibitory activity from the estrogen receptor-mediated genomic effects, we synthesized several compounds structurally related to tamoxifen. Among them, we iden...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn200091w
更新日期：2012-02-15 00:00:00
abstract：:On the basis of the drug-repositioning and redeveloping strategy, first-generation dual-target inhibitors of acetylcholinesterase (AChE) and phosphodiesterase 5 (PDE5) have been recently reported as a potentially novel therapeutic method for the treatment of Alzheimer's disease (AD), and the lead compound 2 has proven...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00014
更新日期：2018-07-18 00:00:00
abstract：:The intramembrane aspartyl protease γ-secretase (GSEC) cleaves single-span transmembrane helices including the C-terminal fragment of the amyloid precursor protein (APP). This substrate is initially cleaved at the ϵ-site followed by successive processing (trimming) events mostly in steps of three amino acids. GSEC is ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00725
更新日期：2019-03-20 00:00:00
