Abstract：
:Glioblastoma (GBM) is characterized by a poor response to conventional chemotherapeutic agents, attributed to the insurgence of drug resistance mechanisms and to the presence of a subpopulation of glioma stem cells (GSCs). GBM cells and GSCs present, among others, an overexpression of antiapoptotic proteins and an inhibition of pro-apoptotic ones, which help to escape apoptosis. Among pro-apoptotic inducers, the Bcl-2 family protein Bax has recently emerged as a promising new target in cancer therapy along with first BAX activators (BAM7, Compound 106, and SMBA1). Herein, a derivative of BAM-7, named BTC-8, was employed to explore the effects of Bax activation in different human GBM cells and in their stem cell subpopulation. BTC-8 inhibited GBM cell proliferation, arrested the cell cycle, and induced apoptosis through the induction of mitochondrial membrane permeabilization. Most importantly, BTC-8 blocked proliferation and self-renewal of GSCs and induced their apoptosis. Notably, BTC-8 was demonstrated to sensitize both GBM cells and GSCs to the alkylating agent Temozolomide. Overall, our findings shed light on the effects and the relative molecular mechanisms related to Bax activation in GBM, and they suggest Bax-targeting compounds as promising therapeutic tools against the GSC reservoir.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Daniele S,Pietrobono D,Costa B,Giustiniano M,La Pietra V,Giacomelli C,La Regina G,Silvestri R,Taliani S,Trincavelli ML,Da Settimo F,Novellino E,Martini C,Marinelli Ldoi
10.1021/acschemneuro.7b00023subject
Has Abstractpub_date
2018-01-17 00:00:00pages
85-99issue
1issn
1948-7193journal_volume
9pub_type
杂志文章abstract：:Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) autophosphorylation at Thr286 and Thr305/Thr306 regulates kinase activity and modulates subcellular targeting and is critical for normal synaptic plasticity and learning and memory. Here, a mass spectrometry-based approach was used to identify Ca(2+)-dependent a...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500337u
更新日期：2015-04-15 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：:Amyloid-beta (Aβ) peptide misfolds into fibrillary aggregates (β-sheet) and is deposited as amyloid plaques in the cellular environment, which severely damages intraneuronal connections leading to Alzheimer's disease (AD) pathogenesis. Furthermore, neurons are rich in tubulin/microtubules, and the intracellular networ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00115
更新日期：2019-05-15 00:00:00
abstract：:Indole and indazole synthetic cannabinoids (SCs) featuring l-valinate or l-tert-leucinate pendant group have recently emerged as prevalent recreational drugs, and their use has been associated with serious adverse health effects. Due to the limited pharmacological data available for these compounds, 5F-AMBICA, 5F-AMB,...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.6b00137
更新日期：2016-09-21 00:00:00
abstract：:The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1-5. In this article, w...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100093f
更新日期：2011-02-16 00:00:00
abstract：:We have developed a novel sampling technique that allows both introduction and removal of fluid from the extracellular space of living tissue. This method is based on the fluidics of push-pull perfusion but flow is driven by electroosmosis. We have applied this method to organotypic hippocampal cultures. A source capi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn4000814
更新日期：2013-05-15 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
pub_type： 杂志文章
doi：10.1021/cn400079y
更新日期：2013-07-17 00:00:00
abstract：:The understanding of the interaction between the membrane of neurons and amyloid-β peptides is of crucial importance to shed light on the mechanism of toxicity in Alzheimer's disease. This paper describes how supercritical angle fluorescence spectroscopy was applied to monitor in real-time the interaction between a su...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00264
更新日期：2019-12-18 00:00:00
abstract：:The development of a noninvasive method for the detection of Alzheimer's disease is of high current interest, which can be critical in early diagnosis and in guiding treatment of the disease. The aggregates of β-amyloid are a pathological hallmark of Alzheimer's disease. Carbohydrates such as gangliosides have been sh...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn3002015
更新日期：2013-04-17 00:00:00
abstract：:We previously reported on the synthesis of substituted phenyl-4-hydroxy-1-piperidyl indole analogues with nanomolar affinity at D2 dopamine receptors, ranging from 10- to 100-fold selective for D2 compared to the D3 dopamine receptor subtype. More recently, we evaluated a panel of aripiprazole analogues, identifying s...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300142q
更新日期：2012-12-19 00:00:00
abstract：:Central norepinephrine (NE) and dopamine (DA) are involved in a variety of physiological functions and behaviors. Accumulating evidence suggests that NE neurons originating from the locus coeruleus (LC) innervate DA neurons of the ventral tegmental area (VTA) and influence VTA-DA neural activity. However, the underlyi...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00078
更新日期：2017-09-20 00:00:00
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
更新日期：2011-05-27 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：: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
更新日期：2020-02-19 00:00:00
abstract：:Dendritic spines are the postsynaptic sites for the majority of excitatory synapses in the mammalian forebrain. While many spines display great stability, others change shape in a matter of seconds to minutes. These rapid alterations in dendritic spine number and size require tight control of the actin cytoskeleton, t...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn100012x
更新日期：2010-05-19 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
pub_type： 杂志文章
doi：10.1021/cn400077d
更新日期：2013-08-21 00:00:00
abstract：:Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00140
更新日期：2017-10-18 00:00:00
abstract：:In humans, genetic defects of the synthesis or regeneration of tetrahydrobiopterin (BH4), an essential cofactor in hydroxylation reactions, are associated with severe neurological disorders. The diagnosis of these conditions relies on the determination of BH4, dihydrobiopterin (BH2), and dihydroneopterin (NH2) in cere...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn4001928
更新日期：2014-07-16 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
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00215
更新日期：2019-08-21 00:00:00
abstract：:Abnormally aggregated tau is the hallmark pathology of tauopathy neurodegenerative disorders and is a target for development of both diagnostic tools and therapeutic strategies across the tauopathy disease spectrum. Development of carbon-11- or fluorine-18-labeled radiotracers with appropriate affinity and specificity...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500103u
更新日期：2014-08-20 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
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00287
更新日期：2016-03-16 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
pub_type： 杂志文章
doi：10.1021/cn100099n
更新日期：2011-08-17 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：: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
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00761
更新日期：2021-01-19 00:00:00
abstract：:A comprehensive survey of kainic acid analogs that have been tested for their biological activity is presented. Specifically, this review (1) gathers and compares over 100 kainoids according to a relative activity scale, (2) exposes structural features required to optimize affinity for kainate receptors, and (3) sugge...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.9b00349
更新日期：2019-10-16 00:00:00
abstract：:The melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors are expressed in the brain and are implicated in the regulation of food intake and energy homeostasis. The endogenous agonist ligands for these receptors (α-, β-, γ-MSH and ACTH) are linear peptides with limited receptor subtype selectivity and metabolic st...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn5000953
更新日期：2014-10-15 00:00:00
abstract：:Interactions between superoxide dismutase-1 (SOD1) and lipid membranes might be directly involved in the toxicity and intercellular propagation of aggregated SOD1 in amyotrophic lateral sclerosis (ALS), but the chemical details of lipid-SOD1 interactions and their effects on SOD1 aggregation remain unclear. This paper...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00086
更新日期：2018-07-18 00:00:00
abstract：:Members of the lysine-specific histone demethylase 5 (KDM5/JARID1) family are known to play important roles in stem cell fate determination. Here, using the KDM5 inhibitor C70 (KDM5-C70), we demonstrated that the histone demethylase activity of the KDM5 enzyme is essential for the repression of astrocytic differentiat...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00613
更新日期：2021-01-22 00:00:00
abstract：:Humanin (HN), a 24-amino acid bioactive peptide, has been shown to increase cell survival of neurons after exposure to Aβ and NMDA-induced toxicity and thus could be beneficial in the treatment of Alzheimer's disease (AD). The neuroprotection by HN is reported to be primarily through its agonist binding properties to ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00350
更新日期：2018-03-21 00:00:00
abstract：:Reversion of protein or peptide aggregation is a formidable task, important in various domains of research at the interface of chemistry, medicine, and nanoscience. A novel class of dipeptides, termed as β-breaker dipeptides (BBDPs), is identified, which can be incorporated into the self-recognizing sequences to gener...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn500064z
更新日期：2014-05-21 00:00:00
