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 reprogramming for inhibiting the aggressive proliferation of glioblastoma cells. Cellular reprogramming converts one differentiated cell type into another type based on the principles of regenerative medicine. In this study, we used cellular reprogramming to investigate whether small molecule mediated reprogramming could convert glioblastoma cells into neurons. We investigated a novel method for reprogramming U87MG human glioblastoma cells into terminally differentiated neurons using a small molecule cocktail consisting of forskolin, ISX9, CHIR99021 I-BET 151, and DAPT. Treating U87MG glioblastoma cells with this cocktail successfully reprogrammed the malignant cells into early neurons over 13 days. The reprogrammed cells displayed morphological and immunofluorescent characteristics associated with neuronal phenotypes. Genetic analysis revealed that the chemical cocktail upregulates the Ngn2, Ascl1, Brn2, and MAP2 genes, resulting in neuronal reprogramming. Furthermore, these cells displayed decreased viability and lacked the ability to form high numbers of tumor-like spheroids. Overall, this study validates the use of a novel small molecule cocktail for reprogramming glioblastoma into nonproliferating neurons.
journal_name
ACS Chem Neuroscijournal_title
ACS chemical neuroscienceauthors
Lee C,Robinson M,Willerth SMdoi
10.1021/acschemneuro.8b00365subject
Has Abstractpub_date
2018-12-19 00:00:00pages
3175-3185issue
12issn
1948-7193journal_volume
9pub_type
杂志文章abstract：:An intracerebral hemorrhage (ICH) is a devastating stroke that results in high mortality and significant disability in survivors. Unfortunately, the underlying mechanisms of this injury are not yet fully understood. After the primary (mechanical) trauma, secondary degenerative events contribute to ongoing cell death i...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00037
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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
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abstract：:γ-Secretase is a multiprotein complex that catalyzes intramembrane proteolysis associated with Alzheimer's disease and cancer. Here, we have developed potent sulfonamide clickable photoaffinity probes that target γ-secretase in vitro and in cells by incorporating various photoreactive groups and walking the clickable ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn300143m
更新日期：2013-02-20 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00224
更新日期：2017-10-18 00:00:00
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journal_title：ACS chemical neuroscience
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doi：10.1021/acschemneuro.6b00164
更新日期：2016-10-19 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00260
更新日期：2018-05-16 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn3001262
更新日期：2012-11-21 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00469
更新日期：2018-07-18 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.7b00014
更新日期：2017-07-19 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00060
更新日期：2015-06-17 00:00:00
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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
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00531
更新日期：2020-11-04 00:00:00
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
更新日期：2020-02-05 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
pub_type： 杂志文章
doi：10.1021/acschemneuro.0c00474
更新日期：2020-09-02 00:00:00
abstract：:We recently reported that AMP-activated protein kinase (AMPK) contributes to zinc-induced neuronal death by inducing Bim, a pro-apoptotic Bcl-2 homology domain 3-only protein, in a liver kinase B1 (LKB1)-dependent manner. Current data suggest AMPK plays key roles in excitotoxicity and ischemic brain injury, with zinc ...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00654
更新日期：2019-05-15 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00527
更新日期：2019-03-20 00:00:00
abstract：:As the intrinsic origin of the hypothesis for β-amyloid (Aβ) from Alzheimer's disease, histidine behaviors were found to play a crucial role in Aβ aggregation. To investigate the histidine behaviors during the early stage of aggregation, Aβ40/42 pentamers with different histidine isomer states were simulated at the at...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00094
更新日期：2019-05-15 00:00:00
abstract：:Parkinson's disease (PD) has long been seen as a disorder caused by degeneration of the dopaminergic system, leading to the classic motor manifestations of the disease. However, there is now overwhelming evidence that PD is more than a disease merely caused by dopamine depletion. It is well-known that a myriad of othe...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章,评审
doi：10.1021/acschemneuro.6b00440
更新日期：2017-05-17 00:00:00
abstract：:The melanocortin system regulates an array of diverse physiological functions including pigmentation, feeding behavior, energy homeostasis, cardiovascular regulation, sexual function, and steroidogenesis. Endogenous melanocortin agonist ligands all possess the minimal messaging tetrapeptide sequence His-Phe-Arg-Trp. B...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00181
更新日期：2018-11-21 00:00:00
abstract：:The Chinese mitten crab (Eriocheir sinensis) is a commercially important crab in China and is usually managed at high stocking densities. Agonistic behavior directly impacts crab integrity, survival, and growth and results in economic losses. In the present study, we evaluated the modulatory effects of serotonin (5-HT...
journal_title：ACS chemical neuroscience
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更新日期：2019-11-20 00:00:00
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journal_title：ACS chemical neuroscience
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更新日期：2019-12-18 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
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更新日期：2011-08-17 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
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00013
更新日期：2018-07-18 00:00:00
abstract：:The nitrocatechol derivatives tolcapone (1) and entacapone (2), used as adjunctive therapy in the treatment of Parkinson's disease, were investigated for their potential to inhibit the tau-derived-hexapeptide 306VQIVYK311. They were compared to small molecules that contain similar pharmacophores including the catechol...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/cn400151a
更新日期：2013-12-18 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：: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
pub_type： 杂志文章
doi：10.1021/acschemneuro.9b00242
更新日期：2020-02-05 00:00:00
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journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00725
更新日期：2019-03-20 00:00:00
abstract：:Baicalein, a flavonoid derived from the roots of Scutellariae baicalensis Georgi, has shown health benefits for an array of human diseases including dementia. The senescence-accelerated mouse prone 8 (SAMP8) strain is extensively used as a senile dementia model. To further investigate the effects of baicalein in SAMP8...
journal_title：ACS chemical neuroscience
pub_type： 杂志文章
doi：10.1021/acschemneuro.8b00074
更新日期：2018-07-18 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
pub_type： 杂志文章
doi：10.1021/acschemneuro.5b00195
更新日期：2015-08-19 00:00:00
