Discovery and Optimization of Triazine Nitrile Inhibitors of Toxoplasma gondii Cathepsin L for the Potential Treatment of Chronic Toxoplasmosis in the CNS.

abstract：:Oligomers of amyloid β-protein (Aβ) are thought to be the proximal toxic agents initiating the neuropathologic process in Alzheimer's disease (AD). Therefore, targeting the self-assembly and oligomerization of Aβ has been an important strategy for designing AD therapeutics. In parallel, research into the metallobiolog...

journal_title：ACS chemical neuroscience

authors： Mason AJ,Hurst I,Malik R,Siddique I,Solomonov I,Sagi I,Klärner FG,Schrader T,Bitan G

更新日期：2020-08-05 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

authors： Oset-Gasque MJ,Marco-Contelles J

更新日期：2018-03-21 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

authors： Robichaud AJ,Engers DW,Lindsley CW,Hopkins CR

更新日期：2011-08-17 00:00:00

abstract：:3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6β-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 doub...

journal_title：ACS chemical neuroscience

authors： Váradi A,Marrone GF,Eans SO,Ganno ML,Subrath JJ,Le Rouzic V,Hunkele A,Pasternak GW,McLaughlin JP,Majumdar S

更新日期：2015-11-18 00:00:00

abstract：:The aggregation of amyloid-β (Aβ) peptide induced by Cu(2+) is a key factor in development of Alzheimer's disease (AD), and metal ion chelation therapy enables treatment of AD. Three CQi (i = 1, 2, and 3 with R = H, Cl, and NO2, respectively) drugs had been verified experimentally to be much stronger inhibitors than t...

journal_title：ACS chemical neuroscience

authors： Dong M,Li H,Hu D,Zhao W,Zhu X,Ai H

更新日期：2016-05-18 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

authors： Mak S,Liu Z,Wu L,Guo B,Luo F,Liu Z,Hu S,Wang J,Cui G,Sun Y,Wang Y,Zhang G,Han Y,Zhang Z

更新日期：2020-02-05 00:00:00

abstract：:An in vitro model of ischemic cerebral stroke [oxygen-glucose deprivation (OGD) for 6 h followed by 24 h reoxygenation (R)] with PC12 cells increases Ca(2+) influx by upregulating native L-type Ca(2+) channels and reactive oxygen species (ROS) generation. This reactive oxygen species generation and increase in intrace...

journal_title：ACS chemical neuroscience

authors： Agrawal M,Kumar V,Singh AK,Kashyap MP,Khanna VK,Siddiqui MA,Pant AB

更新日期：2013-02-20 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

authors： White TL,Gonsalves MA

更新日期：2020-09-02 00:00:00

abstract：:Manganese (Mn) may foster aggregation of alpha-synuclein (αSyn) contributing to the pathogenesis of PD. Here, we examined the influence of αSyn overexpression on distribution and oxidation states of Mn in frozen-hydrated primary midbrain neurons (PMNs) by synchrotron-based X-ray fluorescence (XRF) and X-ray absorption...

journal_title：ACS chemical neuroscience

authors： Dučić T,Carboni E,Lai B,Chen S,Michalke B,Lázaro DF,Outeiro TF,Bähr M,Barski E,Lingor P

更新日期：2015-10-21 00:00:00

abstract：:Gangliosides are biologically important glycolipids widely distributed in vertebrate cells. An important member of the ganglioside family is the monosialylganglioside GM1, which has been suggested as a potential therapeutic for Parkinson's disease. In the current study, a late-stage radiofluorination protocol was deve...

journal_title：ACS chemical neuroscience

authors： Revunov E,Johnström P,Arakawa R,Malmquist J,Jucaite A,Defay T,Takano A,Schou M

更新日期：2020-05-06 00:00:00

abstract：:While fibrillar deposits of hyperphosphorylated protein tau are a key hallmark of several neurodegenerative diseases such as Alzheimer's disease, small oligomers have been speculated to be the key toxic aggregate species. Trivalent metal ions were shown to promote tau oligomer formation in vitro. However, little is kn...

journal_title：ACS chemical neuroscience

authors： Nuebling GS,Plesch E,Ruf VC,Högen T,Lorenzl S,Kamp F,Giese A,Levin J

更新日期：2020-03-18 00:00:00

abstract：:Aβ peptides, the main protein components of Alzheimer's disease (AD) plaques, derive from a proteolytic cleavage of the amyloid precursor protein. Due to heterogeneous cleavage sites, a series of Aβ peptides, including the major and widely studied species Aβ1-40 (Aβ40) and Aβ1-42 (Aβ42), are produced. In addition to t...

journal_title：ACS chemical neuroscience

authors： Tomaselli S,Pagano K,D'Arrigo C,Molinari H,Ragona L

更新日期：2017-04-19 00:00:00

abstract：:Neurotrophins, as important regulators of neural development, function, and survival, have a therapeutic potential to repair damaged neurons. However, a controlled delivery of therapeutic molecules to injured tissue remains one of the greatest challenges facing the translation of novel drug therapeutics field. This st...

journal_title：ACS chemical neuroscience

authors： Kraskiewicz H,Breen B,Sargeant T,McMahon S,Pandit A

更新日期：2013-09-18 00:00:00

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

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

abstract：:Neuroinflammatory processes promote a constellation of neurochemical and hormonal changes resulting in profound effects on motivational states (anhedonia), mood (depression and anxiety disorders), and cognitive function (decrements in learning and memory). The enhancement of immunoregulatory processes, such as increas...

journal_title：ACS chemical neuroscience

authors： Frank MG,Fonken LK,Watkins LR,Maier SF,Lowry CA

更新日期：2019-01-16 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

authors： Devereaux AL,Mercer SL,Cunningham CW

更新日期：2018-10-17 00:00:00

abstract：:The light emission chemistry of firefly luciferase can be harnessed to reveal otherwise invisible biological processes occurring in the brains of live animals. Though powerful, the need for the luciferase substrate D-luciferin to traverse the blood-brain barrier poses limitations on the sensitivity and interpretation ...

journal_title：ACS chemical neuroscience

authors： Mofford DM,Miller SC

更新日期：2015-08-19 00:00:00

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

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

更新日期：2019-02-20 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：:Amyloid-β (Aβ), the main constituent in senile plaques found in the brain of patients with Alzheimer's disease (AD), is considered as a causative factor in AD pathogenesis. The clinical examination of the brains of patients with AD has demonstrated that caspase-3 colocalizes with senile plaques. Cellular studies have ...

journal_title：ACS chemical neuroscience

authors： Chang YJ,Linh NH,Shih YH,Yu HM,Li MS,Chen YR

更新日期：2016-08-17 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：:In our efforts to develop hybrid compounds of curcumin and melatonin as potential disease-modifying agents for Alzheimer's disease (AD), a potent lead hybrid compound, Z-CM-I-1, has been recently identified and biologically characterized in vitro. In this work, we report the in vivo effects of Z-CM-I-1 on AD pathologi...

journal_title：ACS chemical neuroscience

authors： Gerenu G,Liu K,Chojnacki JE,Saathoff JM,Martínez-Martín P,Perry G,Zhu X,Lee HG,Zhang S

更新日期：2015-08-19 00:00:00

abstract：:Glucose-6-phosphate dehydrogenase (G6PD) protects the embryo from endogenous and xenobiotic-enhanced oxidative DNA damage and embryopathies. Here we show in aged mice that G6PD similarly protects against endogenous reactive oxygen species (ROS)-mediated neurodegeneration. In G6PD-normal (G6PD(+/+)) and heterozygous (G...

journal_title：ACS chemical neuroscience

authors： Jeng W,Loniewska MM,Wells PG

更新日期：2013-07-17 00:00:00

abstract：:As the first drug to see widespread use for the treatment of attention deficit hyperactivity disorder (ADHD), methylphenidate was the forerunner and catalyst to the modern era of rapidly increasing diagnosis, treatment, and medication development for this condition. During its often controversial history, it has vario...

journal_title：ACS chemical neuroscience

authors： Wenthur CJ

更新日期：2016-08-17 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：: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

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

更新日期：2020-10-07 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

authors： Santra S,Xu L,Shah M,Johnson M,Dutta A

更新日期：2013-10-16 00:00:00

abstract：:This work describes the use of fluorescence correlation spectroscopy (FCS) and a novel amyloid-binding fluorescent probe, ARCAM 1, to monitor the aggregation of the Alzheimer's disease-associated amyloid β-peptide (Aβ). ARCAM 1 exhibits a large increase in fluorescence emission upon binding to Aβ assemblies, making it...

journal_title：ACS chemical neuroscience

authors： Guan Y,Cao KJ,Cantlon A,Elbel K,Theodorakis EA,Walsh DM,Yang J,Shah JV

更新日期：2015-09-16 00:00:00

abstract：:The clinical benzothiophene SERM (BT-SERM), raloxifene, was compared with estrogens in protection of primary rat neurons against oxygen-glucose deprivation (OGD). Structure-activity relationships for neuroprotection were determined for a family of BT-SERMs displaying a spectrum of ERα and ERβ binding affinity and agon...

journal_title：ACS chemical neuroscience

authors： Abdelhamid R,Luo J,Vandevrede L,Kundu I,Michalsen B,Litosh VA,Schiefer IT,Gherezghiher T,Yao P,Qin Z,Thatcher GR

更新日期：2011-05-18 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