Neural Cell News Volume 11.35 | Sep 6 2017

TOP STORY

Human iPS Cell-Derived Dopaminergic Neurons Function in a Primate Parkinson’s Disease Model

Scientists showed that human induced pluripotent stem cells (iPS) cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of Parkinson’s disease (PD) treated with the neurotoxin MPTP. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum. This effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. [Nature] Abstract | Press Release | Editorial

(Ranked by impact factor of the journal)

LMO1 Synergizes with MYCN to Promote Neuroblastoma Initiation and Metastasis

Investigators showed that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. [Cancer Cell] Abstract

The Neuroprotective Transcription Factor ATF5 Is Decreased and Sequestered into Polyglutamine Inclusions in Huntington’s Disease

Scientists explored whether activating transcription factor-5 (ATF5) is expressed by neurons in human brain both in basal conditions and in Huntington’s disease (HD), where unfolded protein response has been described to be partially impaired due to defective ATF6 processing. Apart from confirming that ATF5 is present in human adult neurons, they report accumulation of ATF5 within the characteristic polyglutamine-containing neuronal nuclear inclusions in brains of HD patients and mice. [Acta Neuropathol] Abstract

MHC Matching Improves Engraftment of iPSC-Derived Neurons in Non-Human Primates

Researchers showed the efficacy of major histocompatibility complex (MHC)-matched allogeneic neural cell grafting in the brain, which is considered a less immune-responsive tissue, using induced pluripotent stem cells (iPSCs) derived from an MHC homozygous cynomolgus macaque. Positron emission tomography imaging revealed neuroinflammation associated with an immune response against MHC-mismatched grafted cells. [Nat Commun] Full Article | Press Release | Editorial

Zika Virus Has Oncolytic Activity against Glioblastoma Stem Cells

The authors explored the use of oncolytic virus therapy against glioblastoma with Zika virus (ZIKV), a flavivirus that induces cell death and differentiation of neural precursor cells in the developing fetus. ZIKV preferentially infected and killed glioblastoma stem cells relative to differentiated tumor progeny or normal neuronal cells. [J Exp Med] Full Article | Press Release 1 | Press Release 2

FOXO3-Mediated Chemo-Protection in High-Stage Neuroblastoma Depends on Wild-Type TP53 and SESN3

Investigators found that endogenous FOXO3 mostly localized to the nucleus upon activation of an ectopic, 4OHT-activated FOXO3(A3)ER fusion protein two of the cell lines underwent apoptosis, whereas in the others FOXO3-activation even increased survival during drug-treatment. In the latter cell type, FOXO3 did not induce the BH3-only protein BCL2L11/BIM due to impaired binding of FOXO3 to the BIM-promoter, but still activated other FOXO3 targets. [Oncogene] Full Article

Bone Morphogenetic Protein Promotes LeX-SSEA1 Expression Thereby Interfering with Neural Precursor and Stem Cell Proliferation

Researchers monitored the expression of the carbohydrate in neonatal and adult neural stem cells (NSCs) and in their progeny. Their results showed that the percentage of immunopositive cells and the levels of LeX-SSEA1 immunoreactivity both increase with postnatal age across all stages of the neural lineage. This was associated with decreased proliferation in precursors including NSCs, which accumulated the carbohydrate at the cell surface while remaining quiescent. [Stem Cells] Abstract

Cyclin-Dependent Kinase 4 Regulates Adult Neural Stem Cell Proliferation and Differentiation in Response to Insulin

Investigators revealed that insulin stimulates proliferation, but not survival or self-renewal, of adult neural stem cells. This effect was mediated by insulin receptor substrate 2 and subsequent activation of the protein kinase B, leading to increased activity of the G1-phase cyclin-dependent kinase 4 and cell cycle progression. [Stem Cells] Abstract

Amlexanox, a Selective Inhibitor of IKBKE, Generates Anti-Tumoral Effects by Disrupting the Hippo Pathway in Human Glioblastoma Cell Lines

The anti-tumoral effects and the underlying mechanisms of amlexanox were investigated. Amlexanox significantly suppressed proliferation and invasion and induced apoptosis in glioblastoma cells. [Cell Death Dis] Full Article

Small Molecule-Based Lineage Switch of Human Adipose-Derived Stem Cells into Neural Stem Cells and Functional GABAergic Neurons

Scientists developed highly efficient induction protocols to generate neural stem cell-like cells, neuron-like cells and GABAergic neuron-like cells from human adipose-derived stem cells via small molecule-mediated inhibition of SMAD signaling without genetic manipulation. All induced cells adopted morphological, molecular and functional features of their bona fide counterparts. [Sci Rep] Full Article

HMGB1/Advanced Glycation End Products (RAGE) Does Not Aggravate Inflammation but Promote Endogenous Neural Stem Cells Differentiation in Spinal Cord Injury

Researchers elucidated the effects of RAGE signaling on the neuronal recovery after spinal cord injury (SCI). They found that neural stem cells co-expressed with RAGE were significantly activated after SCI, while stem cell markers Nestin and SOX-2 were reduced by RAGE blockade. [Sci Rep] Full Article

Stem Cell Transplantation for Huntington’s Diseases

The authors describe methods for obtaining optimal neural stem cells for transplantation-based Huntington’s disease (HD) treatment and the differentiation conditions for the functional GABAergic medium spiny neurons as therapeutic cells. They discuss the valuable gene correction of the disease stem cells by the CRISPR/Cas9 system for HD treatment. [Methods] Abstract

Manipulation of Neural Progenitor Fate through the Oxygen Sensing Pathway

Scientists summarize some studies in an attempt to direct effort towards implementation of best methods to advance the use of neural progenitors from basic development towards clinical application. [Methods] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

Novocure Announces Data Presentations

Novocure announced that four data presentations on Tumor Treating Fields will be presented. Among the highlights is a poster discussion of the overall survival and quality of life data from Novocure’s two Phase III pivotal trials in patients with glioblastoma (GBM), EF-14 in newly diagnosed GBM patients and EF-11 in recurrent GBM patients. [Press release from Novocure discussing research to be presented at the European Society for Medical Oncology (ESMO) 2017 Congress, Madrid] Press Release

Northwestern Mutual Announces $600,000 in New Childhood Cancer Research Grants

Northwestern Mutual, through its Foundation, announced the funding of four new grants supporting childhood cancer research. Through Alex’s Lemonade Stand Foundation’s Young Investigator program, grants are created to support aspiring scientists who are early in their careers and are devoting their lives to finding better treatments and cures for childhood cancer. [Northwestern Mutual] Press Release

Hyundai Hope on Wheels Awards $150,000 Research Grant to the Beckman Research Institute at City of Hope in Honor of National Childhood Cancer Awareness Month

Hyundai Hope On Wheels^® will present The Beckman Research Institute at City of Hope with a $150,000 Hyundai Young Investigator Grant. The grant funds will support the research of principal investigator Dr. Leo David Wang. [Hyundai Hope On Wheels^® (PR Newswire Association LLC.)] Press Release

First Subject Dosed in Phase I Clinical Study of Novel Selective Muscarinic M₄ Agonist in Development to Treat Major Symptoms of Alzheimer’s Disease

Sosei Group Corporation announced that the first healthy subject has been dosed with the first-in-class, selective muscarinic M₄ receptor agonist HTL0016878 in a Phase I clinical study. [Sosei Group Corporation] Press Release

German Federal Joint Committee Announces Decision to Support a Clinical Trial to Study Optune^® for the Treatment of Newly Diagnosed Glioblastoma

Novocure announced that the German Federal Joint Committee has published its decision to support a clinical trial studying Optune for the treatment of newly diagnosed glioblastoma. The proposed trial design will examine the benefit of combining Optune with radiation therapy and temozolomide prior to the initiation of maintenance temozolomide in accordance with Section 137e of the German Healthcare Provision Act. [Novocure] Press Release

Deciphera Pharmaceuticals Announces FDA Orphan Drug Designation for DCC-2618 for the Treatment of Glioblastoma Multiforme and Anaplastic Astrocytoma

Deciphera Pharmaceuticals announced that the FDA has granted orphan drug designation to DCC-2618, the company’s pan-KIT and PDGFRα inhibitor, for the treatment of glioblastoma multiforme and anaplastic astrocytoma. [Deciphera Pharmaceuticals] Press Release

Zydus Receives Final Approval from the USFDA for Donepezil Hydrochloride Tablets

Zydus Cadila has received the final approval from the USFDA to market Donepezil Hydrochloride Tablets, in the strength of 23 mg. The drug is indicated for the treatment of dementia of the Alzheimer’s disease. [Zydus Cadila] Press Release

Researchers Riled by Lack of Detail in Brexit Science Plans

More than one year after UK citizens voted to leave the European Union (EU) and just over two months into ‘Brexit’ negotiations, the British government has finally laid out how it would like to handle scientific relationships with the EU after it leaves the bloc next year. Many scientists are less than impressed. [Nature News] Editorial

Senate Spending Panel Approves $2 Billion Raise for NIH in 2018

A Senate subcommittee approved a $2 billion raise, to $36.1 billion, for the National Institutes of Health (NIH) in the 2018 fiscal year. To the relief of research universities, the Senate draft spending bill would also block a Trump proposal to slash NIH payments to cover the overhead costs of research. [ScienceInsider] Editorial

Researchers Thought Peace in Colombia Would Mean More Science Funding. They Were Wrong

Wearing lab coats and hoisting placards with slogans such as “A country without science is a country without a future,” hundreds of scientists poured into plazas in cities across Colombia. Their beef: a proposed 42% cut to the 2018 budget of Colciencias, the nation’s science ministry in Bogotá, which doles out research grants and supports graduate students. [ScienceInsider] Editorial

Brain Researchers in Uproar over NIH Clinical-Trials Policy

Scientists studying human behavior and cognitive brain function are up in arms over a plan by the US National Institutes of Health (NIH) to classify most studies involving human participants as clinical trials. [Nature News] Editorial

NEW American Society for Cell Biology (ASCB)-European Molecular Biology Organization (EMBO) 2017 Meeting
December 2-6, 2017
Philadelphia, Pennsylvania, United States

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Positions – Circular RNAs and Circadian Rhythms (Brandeis University)

Postdoctoral Positions – Cancer and/or Glioma Stem Cells (Cornell University)

Faculty Members – Neuroscience (Mercer University)

Lead Bioengineer – Parkinson’s Disease Research (Scaled Biolabs Inc.)

Research Associate – Parkinson’s Disease Research (Scaled Biolabs Inc.)

Research Associate – Neuroscience (Thomas Jefferson University)

Postdoctoral Position – Genetic and Viral Causes of Microencephaly (Duke University Medical Center)

Postdoctoral Fellow – Glioblastoma Multiforme (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow/Associate Positions – Neuroscience (State University of New York)

Postdoctoral Fellowship Positions and Principal Investigator – Brain Tumors (University of California, San Francisco)

Postdoctoral Researchers – Glial Cells (University of California, Davis)

Faculty Scientists – Neuroscience (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Neural Regeneration (Johns Hopkins University)

Postdoctoral Fellow – Stem Cell Biology and Neuroscience (University of Texas Health Science Center at Houston)

Biomedical Engineering Faculty Position – Neural Regeneration and Functional Tissue Engineering (Pennsylvania State University)

Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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