Neural Cell News Volume 11.19 | May 17 2017

TOP STORY

Spinal Muscular Atrophy: New Clues to Cause and Treatment

Spinal muscular atrophy (SMA), a neurodegenerative disease that causes progressive muscle wasting and paralysis, may be partly due to abnormalities in the synapses that connect sensory neurons and motor neurons, according to researchers at Columbia University Medical Center. Their study, conducted in mice, also showed that increasing the activity of these synapses alone can alleviate symptoms of SMA. [Press release from Columbia University Medical Center discussing online prepublication in Nature Neuroscience] Press Release | Abstract

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PTEN Regulates Glioblastoma Oncogenesis through Chromatin-Associated Complexes of DAXX and Histone H3.3

Investigators report a novel chromatin-associated function of phosphatase and tensin homolog (PTEN) in complex with the histone chaperone DAXX and the histone variant H3.3. They showed that PTEN interacts with DAXX and, in turn PTEN directly regulates oncogene expression by modulating DAXX-H3.3 association on the chromatin, independently of PTEN enzymatic activity. [Nat Commun] Full Article

Combined HMG-CoA Reductase and Prenylation Inhibition in Treatment of CCM

The authors performed a high-throughput screen to identify Food and Drug Administration-approved drugs or other bioactive compounds that could effectively suppress hyperproliferation of mouse brain primary astrocytes deficient for cerebral cavernous malformations (CCMs). They demonstrated that fluvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA reductase and the N-bisphosphonate zoledronic acid monohydrate, an inhibitor of protein prenylation, act synergistically to reverse outcomes of CCM3 loss in cultured mouse primary astrocytes and in Drosophila glial cells in vivo. [Proc Natl Acad Sci USA] Full Article

Voltage-Gated Na⁺ Currents in Human Dorsal Root Ganglion Neurons

Scientists determined the extent to which the biophysical and pharmacological properties of voltage-gated Na⁺ channels were comparable in rat and human sensory neurons. Their results indicated that while the two major current types, generally referred to as tetrodotoxin (TTX)-sensitive and TTX-resistant were qualitatively similar in neurons from rats and humans, there were several differences that have important implications for drug development as well as the understanding of pain mechanisms. [Elife] Full Article

Dovitinib Enhances Temozolomide Efficacy in Glioblastoma Cells

Researchers used glioblastoma (GB) patient cells and cell lines to show that Dovitinib (Dov) downregulated the stem cell protein Lin28 and its target high mobility group protein A2 (HMGA2). The Dov-induced reduction in pSTAT3^Tyr705 phosphorylation demonstrated that Dov negatively affects the STAT3-LIN28-Let-7-HMGA2 regulatory axis in GB cells. [Mol Oncol] Full Article

ZBP1 Phosphorylation at Serine 181 Regulates Its Dendritic Transport and the Development of Dendritic Trees of Hippocampal Neurons

Investigators found that ZBP1 is phosphorylated at Ser181 in neurons in a mammalian/mechanistic target of rapamycin complex 2-, Src kinase-, and mRNA binding-dependent manner. They found that Ser181 ZBP1 phosphorylation was essential for the proper dendritic branching of hippocampal neurons that were cultured in vitro and for the proper ZBP1 dendritic distribution and motility. [Sci Rep] Full Article

Differentiation of Human Olfactory Bulb-Derived Neural Stem Cell towards Oligodendrocyte Development

Scientists differentiated human olfactory bulb neural stem cells (OBNSCs) into oligodendrocyte precursor cells/oligodendrocytes (OPCs/OLs), and using expression profiling gene, immunocytochemistry and specific protein expression, they highlighted the molecular mechanism(s) underlying differentiation of human OBNSCs into OPCs/OLs. [J Cell Physiol] Abstract

Vesicular Glutamate Transporters Play a Role in Neuronal Differentiation of Cultured SVZ-Derived Neural Precursor Cells

The authors investigated the implication of vesicular glutamate transporters (VGLUTs) in the differentiation of subventricular zone (SVZ)-derived neural precursor cells (NPCs). Their results showed that NPCs express VGLUT1-3 and excitatory amino acid transporters 1-3 both at the mRNA and protein level. Their expression increases during differentiation closely associated with the expression of marker genes. [PLoS One] Full Article

The Ratio of 1/3 Linoleic Acid to Alpha Linolenic Acid Is Optimal for Oligodendrogenesis of Embryonic Neural Stem Cells

Researchers investigated the effect of various concentrations and ratios of linoleic acid (LA) and alpha linolenic acid (ALA), which belong respectively to omega-6 and omega-3 polyunsaturated fatty acids, on the proliferation and differentiation of embryonic neural stem cells. Results showed that low or high concentrations of ALA, but not LA, and the ratio of 1:3 of LA/ALA significantly increased neurospheres size, frequency and cell numbers, in comparison to controls. [Neurosci Lett] Abstract

Huntington Disease as a Neurodevelopmental Disorder and Early Signs of the Disease in Stem Cells

The authors discuss the early molecular pathogenesis of Huntington disease (HD) in pluripotent and neural stem cells, with respect to the neurodevelopmental aspects of HD. [Mol Neurobiol] Full Article

Alzheimer’s Disease, Dementia, and Stem Cell Therapy

Investigators focus on recent advances in stem cell therapies utilizing animal models of Alzheimer’s disease (AD), as well as detailing the human clinical trials of stem cell therapies for AD that are currently undergoing development. [Stem Cell Res Ther] Full Article

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LCT Collaborates with Center for Brain Research to Extend Product Pipeline

Living Cell Technologies Limited (LCT) has initiated a research collaboration with the Centre for Brain Research at the University of Auckland. The research collaboration will explore how LCT’s products can reverse human brain neurodegenerative processes associated with pericytes (and other brain cells), which help sustain the blood-brain barrier and other homeostatic and haemostatic functions in the brain. [Living Cell Technologies Limited] Press Release

Enterin’s RASMET Study Enrolls First Patient with Parkinson’s Disease

Enterin Inc. enrolled the first patient in the RASMET study. The study is a Phase I/IIa randomized, controlled, multicenter study involving patients with Parkinson’s disease and taking place at 12 US sites. The study will establish the safety, tolerability and efficacy of an orally administered synthetic derivative of squalamine, which is not absorbed into the blood stream. [Enterin Inc. (PR Newswire Association LLC.)] Press Release

Biohaven’s Trigriluzole Receives Fast Track Designation from U.S. FDA

Biohaven Pharmaceutical Holding Company Ltd. (Biohaven) announced that the U.S. Food and Drug Administration (FDA) has granted the company Fast Track Designation for Biohaven’s product candidate trigriluzole for the potential treatment of spinocerebellar ataxia. [Biohaven Pharmaceutical Holding Company Ltd.] Press Release

China’s Belt and Road Infrastructure Plan Also Includes Science

China’s plan to make massive investments in land and sea links with global trading partners also includes a little noticed commitment to support science and engineering, including the creation of dozens of new laboratories. [ScienceInsider] Editorial

Trump Officials Act to Tilt Federal Science Boards toward Industry

Critics say that changes to advisory groups at the Environmental Protection Agency and Department of Interior could restrict or paralyze them. [Nature News] Editorial

Biology Needs More Staff Scientists

Most research institutions are essentially collections of independent laboratories, each run by principal investigators who head a team of trainees. This scheme has ancient roots and a track record of success. But it is not the only way to do science. Indeed, for much of modern biomedical research, the traditional organization has become limiting. [Nature News] Editorial

Revamped ‘Anti-Science’ Education Bills in United States Find Success

State and local legislatures in the United States are experimenting with new ways to target the topics taught in science classes, and it seems to be paying dividends. Florida’s legislature approved a bill that would enable residents to challenge what educators teach students. [Nature News] Editorial

NEW Mechanisms of Neurodegeneration
June 14-17, 2017
Heidelberg, Germany

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NEW Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

NEW Postdoctoral Fellow – Neuroendocrine Biology of Metabolism (The Scripps Research Institute)

Research Fellow – Neuroscience and Behavioral Disorders (Duke-NUS Medical School)

Postdoctoral Scientist – Cell Biology (Medical Research Council)

Postdoctoral Position – Molecular Biology (KU Leuven)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Director – BrainHub (Carnegie Mellon University)

Postdoctoral Position(s) – Visual Neuroscience (Yale University)

Postdoctoral Fellow – Spinal Cord Injury Repair (Burke Medical Research Institute Cornell)

Assistant/Associate Professor – Canada Research Chair in Mental Health (University of Alberta)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

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