Neural Cell News Volume 9.17 | May 6 2015

Oxygen and Glucose Deprivation Induces Widespread Alterations in mRNA Translation within 20 Minutes
Using time-resolved ribosome profiling, researchers assessed gene expression levels in a neural cell line, PC12, during the first hour of oxygen and glucose deprivation (OGD). The most substantial alterations occurred within the first 20 minutes of OGD. [Genome Biol] Full Article | Press Release

Notch Activity Modulates the Responsiveness of Neural Progenitors to Sonic Hedgehog Signaling
Interpretation of the Sonic hedgehog (Shh) gradient depends on both the amount of ligand and duration of exposure, but the mechanisms permitting prolonged responses to Shh are not well understood. Researchers demonstrated that Notch signaling plays an essential role in this process, enabling neural progenitors to attain sufficiently high levels of Shh pathway activity needed to direct the ventral-most cell fates. [Dev Cell] Full Article | Graphical Abstract

Protein Phosphatase 2A Inhibition with LB100 Enhances Radiation-Induced Mitotic Catastrophe and Tumor Growth Delay in Glioblastoma
The authors investigated the effects of protein phosphatase 2A inhibition on U251 glioblastoma cells following radiation treatment in vitro and in a xenograft mouse model in vivo. [Mol Cancer Ther] Abstract

Mitogen-Activated Protein Kinase Signaling Pathways Promote Low-Density Lipoprotein Receptor-Related Protein 1-Mediated Internalization of Beta-Amyloid Protein in Primary Cortical Neurons
The authors explored the regulation of mitogen-activated protein kinase signaling pathways on lipoprotein receptor-related protein 1-mediated beta-amyloid protein (Aβ) internalization in neurons. They found that extracellular Aβ1–42 oligomers could be internalized into endosomes/lysosomes and mitochondria in cortical neurons. [Int J Biochem Cell Biol] Abstract

Effects of Cordycepin on the Microglia-Overactivation-Induced Impairments of Growth and Development of Hippocampal Cultured Neurons
Scientists attempted to identify the anti-inflammatory role of cordycepin and its protective effects on the impairments of neural growth and development induced by microglial over-activation. [PLoS One] Full Article

The Methyl Binding Domain 3/Nucleosome Remodelling and Deacetylase Complex Regulates Neural Cell Fate Determination and Terminal Differentiation in the Cerebral Cortex
Researchers showed for the first time that methyl binding domain 3/nucleosome remodelling and deacetylation (MBD3/NuRD) function is essential for normal neurogenesis in mice. Deletion of MBD3, a structural component of the NuRD complex, in the developing mouse central nervous system resulted in reduced cortical thickness, defects in the proper specification of cortical projection neuron subtypes and neonatal lethality. [Neural Dev] Abstract | Full Article

FTY720 Induces Autophagy-Related Apoptosis and Necroptosis in Human Glioblastoma Cells
Scientists found that FTY720 induced extrinsic apoptosis, necroptosis and autophagy in human glioblastoma cells. Inhibition of autophagy by either RNA interference or chemical inhibitors attenuated FTY720-induced apoptosis and necrosis. [Toxicol Lett] Abstract

In Vitro Expansion of U87-MG Human Glioblastoma Cells under Hypoxic Conditions Affects Glucose Metabolism and Subsequent In Vivo Growth
The authors focused on the impact of oxygen conditions during in vitro cell culture on glucose metabolism using 1-¹³C-glucose. Growing U87-MG glioma cells under hypoxic conditions leads to a two- to threefold reduction of labeled glutamine and an accumulation of fructose. [Tumor Biol] Abstract

Activity of Botulinum Neurotoxin Type D (Strain 1873) in Human Neurons
Scientists examined sensitivity of cultured human neurons derived from human induced pluripotent stem cells to botulinum neurotoxin type D (BoNT/D). They indicated that BoNT/D can enter and cleave VAMP 2 in human neurons, but at significantly lower efficiency than other BoNT serotypes. [Toxicon] Abstract

Experimental Advances Towards Neural Regeneration from Induced Stem Cells to Direct In Vivo Reprogramming
The authors highlight the recent studies on in vivo direct reprogramming, focusing on astrocytes conversion to neurons or to neural stem/precursors cells, in the perspective of future therapeutic purposes for neurological disorders. [Mol Neurobiol] Abstract

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Phase I Clinical Trial of Oncolytic Delta-24-RGD (DNX-2401) with Biological Endpoints: Implications for Viro-Immunotherapy
Winner of the Journal on Neuro-Oncology Award, Frederick F. Lang Jr., MD, FAANS, presented his research into Delta-24-RGD. Delta-24-RGD is a new oncolytic virus with a favorable toxicity-profile that is capable of replicating in and killing human glioma cells, and that can produce durable complete-responses in subsets of patients. [Press release from the American Association of Neurological Surgeons (AANS) (Newswise, Inc.) discussing research presented at the 2015 AANS Annual Meeting, Washington D.C.] Press Release

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Paul G. Allen Family Foundation Awards $7.5 Million to Study Brain Cell Growth and Development
The Paul G. Allen Family Foundation announced the award of Allen Distinguished Investigator grants to six groups of researchers with projects at the frontier of one of the most challenging roadblocks in neuroscience: growing mature human brain cells in the laboratory. The projects are funded at a total of $7.5 million over three years. [The Paul G. Allen Family Foundation] Press Release

GliaCure Initiates Phase Ib Dosing in Alzheimer’s Patients
GliaCure announced that it has initiated dosing of Alzheimer’s patients in a Phase Ib clinical trial of its lead product candidate, GC021109, a compound developed as a potential disease-modifying treatment. [GliaCure, Inc.] Press Release

The Myelin Repair Foundation and National Institutes of Health Initiate Clinical Studies of Guanabenz for Treatment of Multiple Sclerosis
The Myelin Repair Foundation (MRF), in partnership with the National Institutes of Health, announced that patients are now being enrolled in a clinical trial conducted to study guanabenz, an FDA-approved drug to treat high blood pressure that was identified by MRF-funded researchers as a potential therapeutic to reduce loss of myelin, in multiple sclerosis patients. [Myelin Repair Foundation] Press Release

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NEW Postdoctoral Fellowship – Modeling of Frontotemporal Dementia Using iPSC (KU Leuven)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Neural Tissue Engineering (Nanyang Technological University)

Faculty Positions (IDG/McGovern Institute for Brain Research at Peking University)

PhD Studentship – Neurobiology (Istituto Italiano di Tecnologia)

Postdoctoral Scientist – Neural Stem Cells (Texas Biomedical Research Institute)

Postdoctoral Positions – Stem Cell Biology (University of Wisconsin – Madison)

Postdoctoral Fellow – Development of the Nervous System and the Origin of Neural Diversity (Columbia University Medical Center)

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