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, cerebrospinal fluid (CSF), or brain extracts remains challenging. We introduce an oligomer-specific (in preference to monomers or fibrils) fluorescence assay based on a conformationally sensitive bis-pyrene-labeled peptide that contains amino acid residues 16-35 of the human amyloid beta protein (pronucleon peptide, PP). This peptide exhibits a shift in fluorescence emission from pyrene excimer to pyrene monomer emission resulting from a conformational change. Specific binding of PP to oligomeric forms of Abeta can be monitored in solution by a change in fluorescence spectrum as well as a change in pyrene monomer fluorescence anisotropy (or polarization). The mechanism of binding and its relation to anisotropy and fluorescence lifetime changes are discussed. The development of a simple, rapid, anisotropy assay for measurement of Abeta oligomers is important for further study of the oligomers' role in AD, and specific detection of oligomers in biological samples, such as cerebrospinal fluid.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Matveeva EG,Rudolph A,Moll JR,Thompson RBdoi
10.1021/cn3001262subject
Has Abstractpub_date
2012-11-21 00:00:00pages
982-7issue
11issn
1948-7193journal_volume
3pub_type
杂志文章abstract：:Aggregation of hyperphosphorylated tau is the hallmark of several tauopathies, including Alzheimer's disease (AD). Although the mechanism underlying tau-associated neuronal damage remains unclear, it is believed that tau hyperphosphorylation is one of the key features in disease progression. A recent study demonstrate...
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：:Exosomes, which are lipid bilayer membrane vesicles, have been implicated as carriers of biological macromolecules. In recent years, the functions of exosomes in the spreading of pathological conversion of proteins among neurons have drawn particular attention in Parkinson's disease research. Extracellular α-synuclein...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.8b00469
更新日期：2019-02-20 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：: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：:The distribution and density of neurons within the brain poses many challenges when making quantitative measurements of neurotransmission in the extracellular space. A volume neurotransmitter is released into the synapse during chemical communication and must diffuse through the extracellular space to an implanted sen...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500020s
更新日期：2015-09-16 00:00:00
abstract：:The efficacy of positive allosteric modulators (PAMs) of the metabotropic glutamate receptor 4 (mGlu4) in preclinical rodent models of Parkinson's disease has been established by a number of groups. Here, we report an advanced preclinically characterized mGlu4 PAM, N-(3-chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00035
更新日期：2016-09-21 00:00:00
abstract：:The nicotinic acetylcholine receptor (nAChR) family, the archetype member of the pentameric ligand-gated ion channels, is ubiquitously distributed in the central and peripheral nervous systems, and its members are the targets for both genetic and acquired forms of neurological disorders. In the central nervous system,...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.9b00041
更新日期：2019-05-15 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：: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 be...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00148
更新日期：2019-05-15 00:00:00
abstract：:Penitrem A, PA, is an indole diterpene alkaloid produced by several fungal species. PA acts as a selective Ca2+-dependent K-channels (Maxi-K, BK) antagonist in brain, causing motor system dysfunctions including tremors and seizures. However, its molecular mechanism at the peripheral nervous system (PNS) is still ambig...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00458
更新日期：2020-11-04 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：: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：:The accumulation and deposition of fibrillar aggregates of α-synuclein (α-syn) into Lewy bodies are the major hallmarks of Parkinson's disease (PD) for which there is no cure yet. Disrupting preformed α-syn fibrils is considered one of the rational therapeutic strategies to combat PD. Experimental studies reported tha...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00598
更新日期：2020-12-16 00:00:00
abstract：:In vivo fast-scan cyclic voltammetry provides high-fidelity recordings of electrically evoked dopamine release in the rat striatum. The evoked responses are suitable targets for numerical modeling because the frequency and duration of the stimulus are exactly known. Responses recorded in the dorsal and ventral striatu...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn5000666
更新日期：2014-09-17 00:00:00
abstract：:N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate receptors that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 and two GluN2 subunits. The four GluN2 subtypes (GluN2A-GluN2D) have distinct functional properties a...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00329
更新日期：2018-02-21 00:00:00
abstract：:The fibrillogenesis of amyloid-β protein (Aβ) is considered a crucial factor in the pathogenesis of Alzheimer's disease (AD). Hence, inhibiting Aβ fibrillogenesis is regarded as the primary therapeutic strategy for the prevention and treatment of AD. However, the development of effective inhibitors against Aβ fibrillo...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00441
更新日期：2019-01-16 00:00:00
abstract：:Pentameric glycine receptors (GlyRs) couple agonist binding to activation of an intrinsic ion channel. Substitution of the R271 residue impairs agonist-induced activation and is associated with the human disease hyperekplexia. On the basis of a homology model of the α1 GlyR, we substituted residues in the vicinity of ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn400134p
更新日期：2013-11-20 00:00:00
abstract：:Alzheimer's disease (AD) is a significant health crisis, and current treatments provide only limited benefits to cognition at the cost of serious side effects. Recently, virtual screening techniques such as ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) have emerged as powerful drug...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00627
更新日期：2021-01-06 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：:The nonmedical (i.e., recreational) misuse of synthetic cannabinoids (SCs) is a worldwide public health problem. When compared to cannabis, the misuse of SCs is associated with a higher incidence of serious adverse effects, suggesting the possible involvement of noncannabinoid sites of action. Here, we find that, unli...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00034
更新日期：2020-05-20 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：:Of the free-living amoebae (FLA) Naegleria fowleri, Balamuthia mandrillaris, and Acanthamoeba spp. are known to cause encephalitis. Coined with the term "brain-eating amoebae" (BEA), infection of the central nervous system with FLA has a high mortality rate. A combination of diagnostic delay, lack of new drug developm...
journal_title：ACS chemical neuroscience
pub_type： 社论
doi：10.1021/acschemneuro.9b00635
更新日期：2020-08-19 00:00:00
abstract：:Phosphodiesterase 10 (PDE10) inhibitors have received much attention as promising therapeutic agents for central nervous system (CNS) disorders such as schizophrenia and Huntington's disease. Recently, a hit compound 1 with a novel chromone scaffold has shown moderate inhibitory activity against PDE10A (IC50 = 500 nM)...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00024
更新日期：2020-04-01 00:00:00
abstract：:As the major psychoactive agent in opium and direct precursor for heroin, morphine is a historically critical molecule in chemical neuroscience. A structurally complex phenanthrene alkaloid produced by Papaver somniferum, morphine has fascinated chemists seeking to disentangle pharmacologically beneficial analgesic ef...
journal_title：ACS chemical neuroscience
pub_type： 历史文章,杂志文章,评审
doi：10.1021/acschemneuro.8b00150
更新日期：2018-10-17 00:00:00
abstract：:This Review describes recent activity in the advancement of ligands for the metabotropic glutamate 4 receptor subtype and their potential utility as central nervous system (CNS) therapeutics. Until recently, there was a paucity of compounds with suitable selectivity and druglike properties to elucidate the value of th...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/cn200043e
更新日期：2011-08-17 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：:α-Synuclein (α-syn) is a 140-amino acid protein that plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. However, the molecular determinants that are responsible for triggering and/or propagating α-syn aggregation and toxicity remain poorly understood. Several studies have...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn200074d
更新日期：2011-11-16 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：:No universally efficacious therapy exists for chronic pain, a disease affecting one-fifth of the global population. An overreliance on the prescription of opioids for chronic pain despite their poor ability to improve function has led to a national opioid crisis. In 2018, the NIH launched a Helping to End Addiction Lo...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00166
更新日期：2019-06-19 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
