Alzheimer's Disease, the "One-Molecule, One-Target" Paradigm, and the Multitarget Directed Ligand Approach.

abstract：:A major challenge in neuroscience is to decipher the logic of neural circuitry and to link it to learning, memory, and behavior. Synaptic transmission is a critical event underlying information processing within neural circuitry. In the extracellular space, the concentrations and distributions of excitatory, inhibitor...

journal_title：ACS chemical neuroscience

authors： Liang R,Broussard GJ,Tian L

更新日期：2015-01-21 00:00:00

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

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

更新日期：2014-07-16 00:00:00

abstract：:Brain-eating amoebae (Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri) can cause opportunistic infections involving the central nervous system. It is troubling that the mortality rate is more than 90% despite advances in antimicrobial chemotherapy over the last few decades. Here, we describe urgent k...

journal_title：ACS chemical neuroscience

authors： Khan NA,Anwar A,Siddiqui R

更新日期：2017-11-15 00:00:00

abstract：:Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation res...

journal_title：ACS chemical neuroscience

authors： Naserkhaki R,Zamanzadeh S,Baharvand H,Nabavi SM,Pakdaman H,Shahbazi S,Vosough M,Ghaedi G,Barzegar A,Mirtorabi D,Hedayatshodeh M,Ehsani E,Falahati M,Hajipour MJ,Shahpasand K

更新日期：2019-03-20 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

authors： Starnowska J,Costante R,Guillemyn K,Popiolek-Barczyk K,Chung NN,Lemieux C,Keresztes A,Van Duppen J,Mollica A,Streicher J,Vanden Broeck J,Schiller PW,Tourwé D,Mika J,Ballet S,Przewlocka B

更新日期：2017-10-18 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

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

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

authors： Tofoleanu F,Brooks BR,Buchete NV

更新日期：2015-03-18 00:00:00

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

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

abstract：:Glioblastoma multiforme, a type of deadly brain cancer, originates most commonly from astrocytes found in the brain. Current multimodal treatments for glioblastoma minimally increase life expectancy, but significant advancements in prognosis have not been made in the past few decades. Here we investigate cellular repr...

journal_title：ACS chemical neuroscience

authors： Lee C,Robinson M,Willerth SM

更新日期：2018-12-19 00:00:00

abstract：:Several chemotherapeutic agents used for cancer treatment induce dose-limiting peripheral neuropathy that compromises patients' quality of life and limits cancer treatment. Recently, mitochondrial dysfunction has been shown to be involved in the mechanism of chemotherapy-induced peripheral neuropathy. SS-20 is a mitoc...

journal_title：ACS chemical neuroscience

authors： Toyama S,Shimoyama N,Szeto HH,Schiller PW,Shimoyama M

更新日期：2018-07-18 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

authors： Poulie CBM,Alcaide A,Krell-Jørgensen M,Larsen Y,Astier E,Bjørn-Yoshimoto WE,Yi F,Syrenne JT,Storgaard M,Nielsen B,Frydenvang KA,Jensen AA,Hansen KB,Pickering DS,Bunch L

更新日期：2019-06-19 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

authors： 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 NR

更新日期：2018-07-18 00:00:00

abstract：:The pathogenesis of Parkinson's disease (PD) is multifactorial event. Combination therapies might be more effective in controlling the disease. Thus, the studies reported were designed to test the hypothesis that gastrodin (GAS)-induced de novo synthesis of nuclear factor E2-related factor 2 (Nrf2) and isorhynchophyll...

journal_title：ACS chemical neuroscience

authors： Li Q,Niu C,Zhang X,Dong M

更新日期：2018-03-21 00:00:00

abstract：:When individual neurons in a circuit contain multiple neuropeptides, these peptides can target different sets of follower neurons. This endows the circuit with a certain degree of flexibility. Here we identified a novel family of peptides, the Aplysia SPTR-Gene Family-Derived peptides (apSPTR-GF-DPs). We demonstrated ...

journal_title：ACS chemical neuroscience

authors： Zhang G,Yuan WD,Vilim FS,Romanova EV,Yu K,Yin SY,Le ZW,Xue YY,Chen TT,Chen GK,Chen SA,Cropper EC,Sweedler JV,Weiss KR,Jing J

更新日期：2018-08-15 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

authors： Yano H,Adhikari P,Naing S,Hoffman AF,Baumann MH,Lupica CR,Shi L

更新日期：2020-05-20 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

authors： Walters SH,Taylor IM,Shu Z,Michael AC

更新日期：2014-09-17 00:00:00

abstract：:Amyloid fibrils are the most distinct components of the plaques associated with various neurodegenerative diseases. Kinetic studies of amyloid fibril formation shed light on the microscopic mechanisms that underlie this process as well as the contributions of internal and external factors to the interplay between diff...

journal_title：ACS chemical neuroscience

authors： Nasir I,Linse S,Cabaleiro-Lago C

更新日期：2015-08-19 00:00:00

abstract：:Post-translational modifications of proteins are ubiquitous in living organisms, as they enable an accurate control of the interactions of these macromolecules. For mechanistic studies, it would be highly advantageous to be able to produce in vitro post-translationally modified proteins with site-specificity. Here, we...

journal_title：ACS chemical neuroscience

authors： Lindstedt PR,Taylor RJ,Bernardes GJL,Vendruscolo M

更新日期：2021-01-19 00:00:00

abstract：:Noncompetitive inhibitors of AMPA receptors have attracted interest in recent years as antiepileptic drugs. However, their development is hindered by a lack of detailed understanding of the protein-inhibitor interaction mechanisms. Recently, structures of AMPA receptor complexes with the structurally dissimilar, nonco...

journal_title：ACS chemical neuroscience

authors： Narangoda C,Sakipov SN,Kurnikova MG

更新日期：2019-11-20 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

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

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

authors： Asadbegi M,Shamloo A

更新日期：2019-11-20 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

authors： Velasquez JC,Goeden N,Herod SM,Bonnin A

更新日期：2016-03-16 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

authors： Yao Y,Tang Y,Wei G

更新日期：2020-12-16 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

authors： Liu F,Wang W,Sang J,Jia L,Lu F

更新日期：2019-01-16 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

authors： Fernández T,Martínez-Serrano A,Cussó L,Desco M,Ramos-Gómez M

更新日期：2018-05-16 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

authors： Sato K,Kuriwaki J,Takahashi K,Saito Y,Oka J,Otani Y,Sha Y,Nakazawa K,Sekino Y,Ohwada T

更新日期：2012-02-15 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

authors： Engers DW,Blobaum AL,Gogliotti RD,Cheung YY,Salovich JM,Garcia-Barrantes PM,Daniels JS,Morrison R,Jones CK,Soars MG,Zhuo X,Hurley J,Macor JE,Bronson JJ,Conn PJ,Lindsley CW,Niswender CM,Hopkins CR

更新日期：2016-09-21 00:00:00

abstract：:We propose a tripartite biochemical mechanism for memory. Three physiologic components are involved, namely, the neuron (individual and circuit), the surrounding neural extracellular matrix, and the various trace metals distributed within the matrix. The binding of a metal cation affects a corresponding nanostructure ...

journal_title：ACS chemical neuroscience

authors： Marx G,Gilon C

更新日期：2012-08-15 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

authors： Shan Z,Cai S,Yu J,Zhang Z,Vallecillo TGM,Serafini MJ,Thomas AM,Pham NYN,Bellampalli SS,Moutal A,Zhou Y,Xu GB,Xu YM,Luo S,Patek M,Streicher JM,Gunatilaka AAL,Khanna R

更新日期：2019-06-19 00:00:00

abstract：:The permeation of the potassium ion (K+) through the selectivity filter (SF) of the large conductance Ca2+-activated potassium (Slo1) channel remains an interesting question to study. Although the mode of K+ entering and leaving the SF has been revealed, the mechanism of K+ passing through the SF is still not clear. I...

journal_title：ACS chemical neuroscience

authors： Guo J,Tan Z,Ji Y

更新日期：2019-08-21 00:00:00