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 defined by differential solvent orientation of the lysine 28 side chain in a constrained loop of serine-asparagine-lysine (cSNK), rarely displayed in molecular dynamics simulations of monomer and fibril ensembles. A mouse monoclonal antibody targeting AβOcSNK recognizes ∼50-60 kDa SDS-resistant soluble Aβ assemblages in AD brain and prolongs the lag phase of Aβ aggregation in vitro. Acute peripheral infusion of a murine IgG1 anti-AβOcSNK in two AD mouse models reduced soluble brain Aβ aggregates by 20-30%. Chronic cSNK peptide immunization of APP/PS1 mice engendered an anti-AβOcSNK IgG1 response without epitope spreading to Aβ monomers or fibrils and was accompanied by preservation of global PSD95 expression and improved cued fear memory. Our data indicate that the oligomer subtype AβOcSNK participates in synaptotoxicity and propagation of Aβ aggregation in vitro and in vivo.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Silverman JM,Gibbs E,Peng X,Martens KM,Balducci C,Wang J,Yousefi M,Cowan CM,Lamour G,Louadi S,Ban Y,Robert J,Stukas S,Forloni G,Hsiung GR,Plotkin SS,Wellington CL,Cashman NRdoi
10.1021/acschemneuro.7b00469subject
Has Abstractpub_date
2018-07-18 00:00:00pages
1591-1606issue
7issn
1948-7193journal_volume
9pub_type
杂志文章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：:We review here recent discoveries in the exciting new field of neuromicrobiology. This field encompasses the interactions between the microbiome and the central nervous system. The microbiome has a tremendous impact on human health. In particular, the gut microbiota may play a key role in many essential processes in h...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.7b00373
更新日期：2018-02-21 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：:The delivery of specific genes into neurons offers a potent approach for treatment of diseases as well as for the study of neuronal cell biology. Here we investigated the capabilities of cationic amino acid based lipid assemblies to act as nonviral gene delivery vectors in primary cultured neurons. An arginine-based l...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn400036j
更新日期：2013-12-18 00:00:00
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
doi：10.1021/cn500110p
更新日期：2014-08-20 00:00:00
abstract：:Lithium has been used for the treatment of mood disorders for decades though the molecular mechanism of its therapeutic action and intracellular targets remain furtive. We report that neurotropic agent Li+ binds to the neuronal calcium sensor, Downstream Regulatory Element Antagonist Modulator (DREAM), with an equilib...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00399
更新日期：2020-09-02 00:00:00
abstract：:Exposure to di-(2-ethylhexyl) phthalate (DEHP), a widely used kind of plasticizer, can result in neurodevelopment impairments and learning and memory disorders. We studied the effects and possible mechanisms of maternal DEHP treatment on hippocampal synaptic plasticity in offspring. Pregnant Wistar rats were randomly ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00612
更新日期：2021-01-20 00:00:00
abstract：:The present experiments employed in vivo microdialysis to characterize the effects of commonly used endocannabinoid clearance inhibitors on basal and depolarization-induced alterations in interstitial endocannabinoid levels in the nucleus accumbens of rat brain. Compounds targeting the putative endocannabinoid transpo...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300036b
更新日期：2012-05-16 00:00:00
abstract：:Proton magnetic spectroscopy (1H-MRS) is a noninvasive imaging technique that allows for the quantification of neurometabolic compounds at millimolar concentrations in the living human brain. This technique has been most often used to assess long-term changes in human brain metabolism in psychiatric disorders, pharmac...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00474
更新日期：2020-09-02 00:00:00
abstract：:Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-l...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00120
更新日期：2020-08-05 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：:The finding that acetylcholinesterase (AChE) colocalizes with β-amyloid (Aβ) and promotes and accelerates Aβ aggregation has renewed an intense interest in developing new multifunctional AChE inhibitors as potential disease-modifying drugs for Alzheimer's therapy. To this end, we have developed a new class of selectiv...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100069c
更新日期：2010-11-17 00:00:00
abstract：:Angiotensin converting enzyme (ACE) is a dipeptidyl peptidase transmembrane bound enzyme. Generally, ACE inhibitors are used for the cardiovascular disorders. ACE inhibitors are primary agents for the management of hypertension, so these cannot be avoided for further use. The present Review focuses on the implications...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn500363g
更新日期：2015-04-15 00:00:00
abstract：:Quaternary ammonium analogues of atropine that are unable to cross the blood-brain barrier are used to alleviate peripheral muscarinic toxicity in animal models of epilepsy produced by systemic administration of pilocarpine or diisopropylfluorophosphate (DFP). Currently, methylatropine is the most popular and potent o...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00334
更新日期：2017-04-19 00:00:00
abstract：:Metal-ion misregulation and oxidative stress continue to be components of the continually evolving hypothesis describing the molecular origins of Alzheimer's disease. Therefore, these features are viable targets for synthetic chemists to explore through hybridizations of metal-binding ligands and antioxidant units. To...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00184
更新日期：2017-11-15 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：: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：:Amyloid beta (Aβ) aggregation is the key trait responsible for the pathological devastation caused by Alzheimer's disease (AD). Among the various pathways of multifaceted toxicity exhibited by Aβ aggregates in neuronal cells, generation of reactive oxygen species (ROS) by Aβ-CuII complex and mitochondrial damage are p...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00033
更新日期：2018-06-20 00:00:00
abstract：:Mutations in the SOD1 gene are associated with some forms of familial amyotrophic lateral sclerosis (fALS). There are more than 150 different mutations in the SOD1 gene that have various effects on the copper-zinc superoxide dismutase (SOD1) enzyme structure, including the loss of metal binding and a decrease in dimer...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00527
更新日期：2019-03-20 00:00:00
abstract：: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 r...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00239
更新日期：2020-06-17 00:00:00
abstract：:A hallmark of Alzheimer's disease (AD) is the formation of senile plaques comprised of the β-amyloid (Aβ) peptide. Aβ fibrillization is a complex nucleation-dependent process involving a variety of metastable intermediate aggregates and features the formation of inter- and intramolecular salt bridges involving lysine ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00483
更新日期：2020-01-15 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：:Biomarkers which are indicative of acute physiological and emotional states are studied in a number of different areas in cognitive neuroscience. Currently, many cognitive studies are conducted based on programmed tasks followed by timed biofluid sampling, central laboratory processing, and followed by data analysis. ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300159e
更新日期：2013-03-20 00:00:00
abstract：:Vesicular acetylcholine transporter (VAChT) is a member of the major facilitator superfamily (MFS). It contains conserved sequence motifs originally defined in the bacterial multidrug resistance transporter family of the MFS. Motif C (GSLV(227) A(228)PPFGGIL) is located at the C-terminal end of transmembrane helix 5 (...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn900033s
更新日期：2010-05-19 00:00:00
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：: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：:In this article, we have demonstrated the in vivo efficacy of D-512 and D-440 in a 6-OHDA-induced unilaterally lesioned rat model experiment, a Parkinson's disease animal model. D-512 is a novel highly potent D2/D3 agonist, and D-440 is a novel highly selective D3 agonist. We evaluated the neuroprotective properties o...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn400106n
更新日期：2013-10-16 00:00:00
abstract：:Recreational consumption of synthetic cannabinoid receptor agonists (SCRAs) is a growing crisis in public health in many parts of the world. AMB-FUBINACA is a member of this class of drugs and is responsible for a large proportion of SCRA-related toxicity both in New Zealand and internationally. Strikingly, little is ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00429
更新日期：2019-10-16 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：:Bromoalkaloids are secondary metabolites with a demonstrated high activity in several therapeutic areas. In this research, we probe the neuroprotective and antioxidant activities of hymenialdisine and hymenin. Both structures were tested in an oxidative stress cellular model, consisting of cortical neurons that are in...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500258c
更新日期：2015-02-18 00:00:00
