当前位置： SCI文献检索 > ACS Chemical Neuroscience期刊下所有文献 > Structure-activity relationships in peptide modulators of β-amyloid protein aggregation: variation in α,α-disubstitution results in altered aggregate size and morphology.

Structure-activity relationships in peptide modulators of β-amyloid protein aggregation: variation in α,α-disubstitution results in altered aggregate size and morphology.

Abstract：

:Neuronal cytotoxicity observed in Alzheimer's disease (AD) is linked to the aggregation of β-amyloid peptide (Aβ) into toxic forms. Increasing evidence points to oligomeric materials as the neurotoxic species, not Aβ fibrils; disruption or inhibition of Aβ self-assembly into oligomeric or fibrillar forms remains a viable therapeutic strategy to reduce Aβ neurotoxicity. We describe the synthesis and characterization of amyloid aggregation mitigating peptides (AAMPs) whose structure is based on the Aβ "hydrophobic core" Aβ(17-20), with α,α-disubstituted amino acids (ααAAs) added into this core as potential disrupting agents of fibril self-assembly. The number, positional distribution, and side-chain functionality of ααAAs incorporated into the AAMP sequence were found to influence the resultant aggregate morphology as indicated by ex situ experiments using atomic force microscopy (AFM) and transmission electron microscopy (TEM). For instance, AAMP-5, incorporating a sterically hindered ααAA with a diisobutyl side chain in the core sequence, disrupted Aβ(1-40) fibril formation. However, AAMP-6, with a less sterically hindered ααAA with a dipropyl side chain, altered fibril morphology, producing shorter and larger sized fibrils (compared with those of Aβ(1-40)). Remarkably, ααAA-AAMPs caused disassembly of existing Aβ fibrils to produce either spherical aggregates or protofibrillar structures, suggesting the existence of equilibrium between fibrils and prefibrillar structures.

journal_name

ACS Chem Neurosci

journal_title

ACS chemical neuroscience

authors

Bett CK,Ngunjiri JN,Serem WK,Fontenot KR,Hammer RP,McCarley RL,Garno JC

doi

10.1021/cn100045q

subject

Has Abstract

pub_date

2010-09-15 00:00:00

pages

608-26

issue

9

issn

1948-7193

journal_volume

1

pub_type

杂志文章

相关文献

ACS Chemical Neuroscience文献大全
  • A Review of Single-Nucleotide Polymorphisms in Orexigenic Neuropeptides Targeting G Protein-Coupled Receptors.

    abstract：:Many physiological pathways are involved in appetite, food intake, and the maintenance of energy homeostasis. In particular, neuropeptides within the central nervous system have been demonstrated to be critical signaling molecules for modulating appetite. Both anorexigenic (appetite-decreasing) and orexigenic (appetit...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/acschemneuro.8b00151

    authors： Ericson MD,Haskell-Luevano C

    更新日期：2018-06-20 00:00:00

  • Microglia-Based Phenotypic Screening Identifies a Novel Inhibitor of Neuroinflammation Effective in Alzheimer's Disease Models.

    abstract：:Currently, anti-AD drug discovery using target-based approaches is extremely challenging due to unclear etiology of AD and absence of validated therapeutic protein targets. Neuronal death, regardless of causes, plays a key role in AD progression, and it is directly linked to neuroinflammation. Meanwhile, phenotypic sc...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.6b00125

    authors： Zhou W,Zhong G,Fu S,Xie H,Chi T,Li L,Rao X,Zeng S,Xu D,Wang H,Sheng G,Ji X,Liu X,Ji X,Wu D,Zou L,Tortorella M,Zhang K,Hu W

    更新日期：2016-11-16 00:00:00

  • Correlation between Cellular Uptake and Cytotoxicity of Fragmented α-Synuclein Amyloid Fibrils Suggests Intracellular Basis for Toxicity.

    abstract：:Aggregation and intracellular deposition of the protein α-synuclein is an underlying characteristic of Parkinson's disease. α-Synuclein assemblies also undergo cell-cell spreading, facilitating propagation of their cellular pathology. Understanding how cellular interactions and uptake of extracellular α-synuclein asse...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00562

    authors： Zhang X,Wesén E,Kumar R,Bernson D,Gallud A,Paul A,Wittung-Stafshede P,Esbjörner EK

    更新日期：2020-02-05 00:00:00

  • A Multifunctional Chemical Agent as an Attenuator of Amyloid Burden and Neuroinflammation in Alzheimer's Disease.

    abstract：:Alzheimer's disease (AD) is the most common neurodegenerative disease, and its main hallmark is the deposition of amyloid beta (Aβ) peptides. However, several clinical trials focusing on Aβ-targeting agents have failed recently, and thus new therapeutic leads are focusing on alternate targets such as tau protein patho...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.0c00114

    authors： Cho HJ,Sharma AK,Zhang Y,Gross ML,Mirica LM

    更新日期：2020-05-20 00:00:00

  • In Utero Exposure to Citalopram Mitigates Maternal Stress Effects on Fetal Brain Development.

    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

    doi：10.1021/acschemneuro.9b00180

    authors： Velasquez JC,Zhao Q,Chan Y,Galindo LCM,Simasotchi C,Wu D,Hou Z,Herod SM,Oberlander TF,Gil S,Fournier T,Burd I,Andrews AM,Bonnin A

    更新日期：2019-07-17 00:00:00

  • Water-soluble mmp-9 inhibitor prodrug generates active metabolites that cross the blood-brain barrier.

    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

    authors： Song W,Peng Z,Gooyit M,Suckow MA,Schroeder VA,Wolter WR,Lee M,Ikejiri M,Cui J,Gu Z,Chang M

    更新日期：2013-08-21 00:00:00

  • Identification of a Novel Multifunctional Ligand for Simultaneous Inhibition of Amyloid-Beta (Aβ42) and Chelation of Zinc Metal Ion.

    abstract：:Zinc binding to β-amyloid structure could promote amyloid-β aggregation, as well as reactive oxygen species (ROS) production, as suggested in many experimental and theoretical studies. Therefore, the introduction of multifunctional drugs capable of chelating zinc metal ion and inhibiting Aβ aggregation is a promising ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00468

    authors： Asadbegi M,Shamloo A

    更新日期：2019-11-20 00:00:00

  • Increased Brain Exposure of an Alpha-Synuclein Fibrillization Modulator by Utilization of an Activated Ester Prodrug Strategy.

    abstract：:Previous work in our laboratories has identified a series of peptidomimetic 2-pyridone molecules as modulators of alpha-synuclein (α-syn) fibrillization in vitro. As a first step toward developing molecules from this scaffold as positron emission tomography imaging agents, we were interested in evaluating their blood-...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.8b00236

    authors： Cairns AG,Vazquez-Romero A,Mahdi Moein M,Ådén J,Elmore CS,Takano A,Arakawa R,Varrone A,Almqvist F,Schou M

    更新日期：2018-11-21 00:00:00

  • Mimicking biological design and computing principles in artificial olfaction.

    abstract：:Biology has inspired solutions to many engineering problems, including chemical sensing. Modern approaches to chemical sensing have been based on the biological principle of combining cross-selective chemical sensors with a pattern recognition engine to identify odors. Here, we review some recent advances made in mimi...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn200027r

    authors： Raman B,Stopfer M,Semancik S

    更新日期：2011-05-27 00:00:00

  • Diverse Effects of Gut-Derived Serotonin in Intestinal Inflammation.

    abstract：:The gut is the largest producer of serotonin or 5-hydroxytryptamine (5-HT) in the human body, and 5-HT has been recognized as an important signaling molecule in the gut for decades. There are two distinct sources of enteric 5-HT. Mucosal 5-HT is predominantly produced by enterochromaffin (EC) cells of the gastrointest...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/acschemneuro.6b00414

    authors： Shajib MS,Baranov A,Khan WI

    更新日期：2017-05-17 00:00:00

  • The APOE ε4 Allele Is Associated with Lower Selenium Levels in the Brain: Implications for Alzheimer's Disease.

    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

    authors： R Cardoso B,Hare DJ,Lind M,McLean CA,Volitakis I,Laws SM,Masters CL,Bush AI,Roberts BR

    更新日期：2017-07-19 00:00:00

  • Deciphering the Mechanism of the Anti-Hypertensive Effect of Isorhynchophylline by Targeting Neurotransmitters Metabolism of Hypothalamus in Spontaneously Hypertensive Rats.

    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

    authors： Li Y,Yu R,Zhang D,Yang W,Hou Q,Li Y,Jiang H

    更新日期：2020-06-03 00:00:00

  • Histamine H3 receptor activation counteracts adenosine A2A receptor-mediated enhancement of depolarization-evoked [3H]-GABA release from rat globus pallidus synaptosomes.

    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

    authors： Morales-Figueroa GE,Márquez-Gómez R,González-Pantoja R,Escamilla-Sánchez J,Arias-Montaño JA

    更新日期：2014-08-20 00:00:00

  • Neuron Activity Dependent Redox Compartmentation Revealed with a Second Generation Red-Shifted Ratiometric Sensor.

    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

    authors： Radhakrishnan S,Norley J,Wendt S,LeRoy N,Hall H,Norcross S,Doan S,Snaider J,MacVicar BA,Weake VM,Huang L,Tantama M

    更新日期：2020-09-02 00:00:00

  • A small linear peptide encompassing the NGF N-terminus partly mimics the biological activities of the entire neurotrophin in PC12 cells.

    abstract：:Ever since the discovery of its neurite growth promoting activity in sympathetic and sensory ganglia, nerve growth factor (NGF) became the prototype of the large family of neurotrophins. The use of primary cultures and clonal cell lines has revealed several distinct actions of NGF and other neurotrophins. Among severa...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.5b00069

    authors： Travaglia A,Pietropaolo A,Di Martino R,Nicoletti VG,La Mendola D,Calissano P,Rizzarelli E

    更新日期：2015-08-19 00:00:00

  • Neuro-Compatible Metabolic Glycan Labeling of Primary Hippocampal Neurons in Noncontact, Sandwich-Type Neuron-Astrocyte Coculture.

    abstract：:Glycans are intimately involved in several facets of neuronal development and neuropathology. However, the metabolic labeling of surface glycans in primary neurons is a difficult task because of the neurotoxicity of unnatural monosaccharides that are used as a metabolic precursor, hindering the progress of metabolic e...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.7b00300

    authors： Choi JY,Park M,Cho H,Kim MH,Kang K,Choi IS

    更新日期：2017-12-20 00:00:00

  • Recent Advances in Virtual Screening for Cholinesterase Inhibitors.

    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

    authors： Miles JA,Ross BP

    更新日期：2021-01-06 00:00:00

  • Iron Dysregulation in Parkinson's Disease: Focused on the Autophagy-Lysosome Pathway.

    abstract：:Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by dopaminergic neuron loss in the substantia nigra pars compacta (SNpc). Although both iron accumulation and a defective autophagy-lysosome pathway contribute to the pathological development of PD, the connection between...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章,评审

    doi：10.1021/acschemneuro.8b00390

    authors： Chen LL,Huang YJ,Cui JT,Song N,Xie J

    更新日期：2019-02-20 00:00:00

  • DARK Classics in Chemical Neuroscience: Opium, a Historical Perspective.

    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

    authors： Presley CC,Lindsley CW

    更新日期：2018-10-17 00:00:00

  • Identification of Novel 1-O-Substituted Aporphine Analogues as Potent 5-HT2C Receptor Agonists.

    abstract：:The 5-HT2C receptor has emerged as a promising target in the treatment of a variety of central nervous system disorders. We have first identified aporphines as a new class of 5-HT2C receptor agonists. Structure-activity relationship results indicate that the aporphine core may be required for 5-HT2C receptor activity,...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00563

    authors： Mao Q,Zhang B,Li W,Tian S,Shui W,Ye N

    更新日期：2020-02-19 00:00:00

  • Olive Oil Lignan (+)-Acetoxypinoresinol Peripheral Motor and Neuronal Protection against the Tremorgenic Mycotoxin Penitrem A Toxicity via STAT1 Pathway.

    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

    authors： Qusa MH,Abdelwahed KS,Meyer SA,El Sayed KA

    更新日期：2020-11-04 00:00:00

  • Delivery of Dual Drug Loaded Lipid Based Nanoparticles across the Blood-Brain Barrier Impart Enhanced Neuroprotection in a Rotenone Induced Mouse Model of Parkinson's Disease.

    abstract：:Parkinson's disease (PD) is the most widespread form of dementia where there is an age related degeneration of dopaminergic neurons in the substantia nigra region of the brain. Accumulation of α-synuclein (αS) protein aggregate, mitochondrial dysfunction, oxidative stress, and neuronal cell death are the pathological ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.6b00207

    authors： Kundu P,Das M,Tripathy K,Sahoo SK

    更新日期：2016-12-21 00:00:00

  • Pair of Residue Substitutions at the Outer Mouth of the Channel Pore Act as Inputs for a Boolean Logic "OR" Gate Based on the Glycine Receptor.

    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

    authors： Han L,Shan Q

    更新日期：2020-10-21 00:00:00

  • Unraveling the Role of Receptor for Advanced Glycation End Products (RAGE) and Its Ligands in Myasthenia Gravis.

    abstract：:Myasthenia gravis (MG) is an autoimmune T cell-dependent B cell-mediated disorder of the neuromuscular junction (NMJ) characterized by fluctuating skeletal muscle weakness, most commonly attributed to pathogenic autoantibodies against postsynaptic nicotinic acetylcholine receptors (AChRs). Although MG pathogenesis is ...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.9b00678

    authors： Angelopoulou E,Paudel YN,Piperi C

    更新日期：2020-03-04 00:00:00

  • Improved Calibration of Voltammetric Sensors for Studying Pharmacological Effects on Dopamine Transporter Kinetics in Vivo.

    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

    authors： Atcherley CW,Laude ND,Monroe EB,Wood KM,Hashemi P,Heien ML

    更新日期：2015-09-16 00:00:00

  • Development of a new photochromic ion channel blocker via azologization of fomocaine.

    abstract：:Photochromic blockers of voltage gated ion channels are powerful tools for the control of neuronal systems with high spatial and temporal precision. We now introduce fotocaine, a new type of photochromic channel blocker based on the long-lasting anesthetic fomocaine. Fotocaine is readily taken up by neurons in brain s...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/cn500070w

    authors： Schoenberger M,Damijonaitis A,Zhang Z,Nagel D,Trauner D

    更新日期：2014-07-16 00:00:00

  • Green Tea Extracts EGCG and EGC Display Distinct Mechanisms in Disrupting Aβ42 Protofibril.

    abstract：:The amyloid beta (Aβ) fibrillar aggregate is the hallmark of Alzheimer's disease (AD). Disassembling preformed fibril or inhibiting Aβ aggregation is considered as a therapeutic strategy for AD. Increasing evidence shows that green tea extracts, epigallocatechin-3-gallate (EGCG, containing an extra gallic acid ester g...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.0c00277

    authors： Zhan C,Chen Y,Tang Y,Wei G

    更新日期：2020-06-17 00:00:00

  • (3-Cyano-5-fluorophenyl)biaryl negative allosteric modulators of mGlu(5): Discovery of a new tool compound with activity in the OSS mouse model of addiction.

    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

    authors： Lindsley CW,Bates BS,Menon UN,Jadhav SB,Kane AS,Jones CK,Rodriguez AL,Conn PJ,Olsen CM,Winder DG,Emmitte KA

    更新日期：2011-08-17 00:00:00

  • Irrigation System and COVID-19 Recurrence: A Potential Risk Factor in the Transmission of SARS-CoV-2.

    abstract：:Several lines of evidence suggest the presence of severe acute respiratory coronavirus-2 (SARS-CoV-2) in wastewater. The use of sewage water for irrigation is common in many developing countries, and it is only partially treated in the majority of countries with less than 10% of collected wastewater receiving any form...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.0c00570

    authors： Siddiqui R,Khamis M,Ibrahim T,Khan NA

    更新日期：2020-10-07 00:00:00

  • A Difluoroboron β-Diketonate Probe Shows "Turn-on" Near-Infrared Fluorescence Specific for Tau Fibrils.

    abstract：:Tau aggregation in neuronal cells has recently received significant attention as a robust predictor of the progression of Alzheimer's disease (AD) because of its proven correlation with the degree of cognitive impairment in AD patients. Accordingly, noninvasive imaging of tau aggregates has been highlighted as a promi...

    journal_title：ACS chemical neuroscience

    pub_type： 杂志文章

    doi：10.1021/acschemneuro.7b00224

    authors： Park KS,Kim MK,Seo Y,Ha T,Yoo K,Hyeon SJ,Hwang YJ,Lee J,Ryu H,Choo H,Chong Y

    更新日期：2017-10-18 00:00:00