Neural Cell News Volume 12.38 | Sep 26 2018

TOP STORY

Direct Induction of Microtubule Branching by Microtubule Nucleation Factor SSNA1

Scientists found that SSNA1 localized at axon branching sites and had a key role in neuronal development. SSNA1 mutants that abolished microtubule branching in vitro also failed to promote axon development and branching when overexpressed in neurons. [Nat Cell Biol] Abstract | Press Release

(Ranked by impact factor of the journal)

ASTN2 Modulates Synaptic Strength by Trafficking and Degradation of Surface Proteins

Researchers demonstrated that ASTN2 bound to and regulated the surface expression of multiple synaptic proteins in postmigratory neurons by endocytosis, resulting in modulation of synaptic activity. In cerebellar Purkinje cells, by immunogold electron microscopy, ASTN2 localized primarily to endocytic and autophagocytic vesicles in the cell soma and in subsets of dendritic spines. [Proc Natl Acad Sci USA] Full Article | Press Release

Small Molecule Inhibits α-Synuclein Aggregation, Disrupts Amyloid Fibrils, and Prevents Degeneration of Dopaminergic Neurons

SynuClean-D significantly reduced the in vitro aggregation of wild-type α-synuclein and the familiar A30P and H50Q variants in a substoichiometric molar ratio. The compound prevented fibril propagation in protein-misfolding cyclic amplification assays and decreases the number of α-synuclein inclusions in human neuroglioma cells. [Proc Natl Acad Sci USA] Abstract | Press Release

Single-Cell RNA-Seq Uncovers a Robust Transcriptional Response to Morphine by Glia

Scientists uncovered unique morphine-dependent transcriptional responses by oligodendrocytes and astrocytes. They revealed a large cohort of morphine-regulated genes. The affected genes were enriched for roles in cellular pathways intimately linked to oligodendrocyte maturation and myelination, including the unfolded protein response. [Cell Rep] Full Article | Graphical Abstract

Stochastic Gene Choice during Cellular Differentiation

Investigators introduced a simple measure to quantify this interdependence in gene expression and differentiated mouse embryonic stem cells to neurons to measure the single-cell expression of the gene isoforms in the protocadherin cluster, a key component of neuronal diversity. [Cell Rep] Full Article | Graphical Abstract

CD163, a Novel Therapeutic Target, Regulates the Proliferation and Stemness of Glioma Cells via Casein Kinase 2

The loss of CD163 expression inhibited both cell cycle progression and the proliferation of glioblastoma multiforme cell lines and primary glioma cells. CD163 interacted directly with casein kinase 2 (CK2) and CD163 silencing reduced AKT/GSK3β/β-catenin/cyclin D1 pathway activity via CK2. [Oncogene] Abstract

Cytoplasmic Dynein Regulates the Subcellular Localization of Sphingosine Kinase 2 to Elicit Tumor-Suppressive Functions in Glioblastoma

Low cytoplasmic dynein 1 (DYNC1I1) expression in glioblastoma (GBM) cells coincided with more SK2 localized to the plasma membrane, where it has been recently implicated in oncogenesis. Re-expression of DYNC1I1 reduced plasma membrane-localized SK2 and extracellular S1P formation, and decreased GBM tumor growth and tumor-associated angiogenesis in vivo. [Oncogene] Full Article

Inhibition of Glioblastoma Cell Proliferation, Invasion, and Mechanism of Action of a Novel Hydroxamic Acid Hybrid Molecule

Researchers showed properties of a novel hybrid molecule, sahaquine, which selectively inhibited cytoplasmic histone deacetylase 6 (HDAC6) at nanomolar concentrations without markedly suppressing class I HDACs. Inhibition of HDAC6 led to significant α-tubulin acetylation, thereby impairing cytoskeletal organization in glioblastoma cells. [Cell Death Discov] Full Article

VDAC2 Interacts with PFKP to Regulate Glucose Metabolism and Phenotypic Reprogramming of Glioma Stem Cells

Disruption of voltage-dependent anion channel 2 (VDAC2) induced dedifferentiation of non-stem tumor cells to acquire glioma stem cell (GSC) features, including the enhanced self-renewal, preferential expression of GSC markers, and increased tumorigenicity. Enforced expression of VDAC2 impaired the self-renewal and highly tumorigenic properties of GSCs. [Cell Death Dis] Full Article

Proscillaridin A Exerts Anti-tumor Effects through GSK3β Activation and Alteration of Microtubule Dynamics in Glioblastoma

Proscillaridin A (ProA) displayed cytotoxic activity on tumor and stem-like cells grown in 2D and 3D culture, but not on healthy cells as astrocytes or oligodendrocytes. Even at sub-cytotoxic concentration, ProA impaired cell migration and disturbed EB1 accumulation at microtubule (MT) plus-ends and MT dynamics instability. [Cell Death Dis] Full Article

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A New Era for Understanding Amyloid Structures and Disease

The authors discuss how amyloid structure may affect the ability of fibrils to spread to different sites in the cell and between organisms in a prion-like manner, along with their roles in disease. These molecular insights will aid in understanding the development and spread of amyloid diseases and are inspiring new strategies for therapeutic intervention. [Nat Rev Mol Cell Biol] Abstract

Microglia in Neurodegeneration

Injury to neurons in Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases, as well as in amyotrophic lateral sclerosis, frontotemporal dementia, and chronic traumatic encephalopathy, results from disruption of the sentinel or housekeeping functions and dysregulation of the defense function and neuroinflammation. Initiation or exacerbation of neurodegeneration results from an imbalance between these microglial functions; correcting such imbalance may be a potential mode for therapy. [Nat Neurosci] Abstract

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

ACADIA Pharmaceuticals to Present at the 2018 Cantor Global Healthcare Conference on October 2, 2018

ACADIA Pharmaceuticals Inc. announced that it will present at the 2018 Cantor Global Healthcare Conference. A live webcast of ACADIA’s presentation will be accessible on the company’s website. [Press release from ACADIA Pharmaceuticals Inc. discussing research to be presented at the 2018 Cantor Global Healthcare Conference, New York] Press Release

Newron Pharmaceuticals to Present at the 2018 Cantor Global Healthcare Conference in New York

Newron Pharmaceuticals S.p.A. announced that Stefan Weber, CEO, will present at the 2018 Cantor Global Healthcare Conference. [Press release from Newron Pharmaceuticals S.p.A. (Business Wire, Inc.) discussing research to be presented at the 2018 Cantor Global Healthcare Conference, New York] Press Release

Genervon Presents Mechanisms of Actions in Alzheimer’s Disease, Including Results Confirming that GM6 Attenuates Alzheimer’s Disease in Mouse Model, in Part by Reducing Inflammation

Genervon’s research team reported new findings that its drug candidate GM6 attenuates Alzheimer’s disease (AD) in an early AD transgenic APP mice model. [Press release from Genervon Biopharmaceuticals, LLC. discussing research presented at the New York Academy of Science Symposium, New York] Press Release

Tocagen Announces Early Completion of Enrollment in Toca 5 Pivotal Phase III Brain Cancer Trial

Tocagen Inc. announced that it has completed the planned enrollment of 380 patients in the global Toca 5 pivotal Phase III trial approximately three months ahead of schedule. Toca 5 is a randomized, multi-center study evaluating the safety and efficacy of Toca 511 & Toca FC compared to standard of care in patients undergoing resection for recurrent high grade glioma. [Tocagen] Press Release

Cerevance Announces First-in-Human Dosing of CVN424 for the Treatment of Parkinson’s Disease

Cerevance announced the start of dosing in a Phase I first-in-human clinical trial of CVN424, an oral compound being developed for symptomatic treatment of Parkinson’s disease. This first-in-class compound modulates a novel protein target selectively expressed in an important class of dopamine-responsive neurons in the striatum. [Cerevance, Inc.] Press Release

NIH Funds UNC Study to Investigate Maternal-Fetal Transmission of Zika

Researchers at the University of North Carolina (UNC) at Chapel Hill and collaborators in Nicaragua have been given a five-year, $2.7 million R01 award from the U.S. National Institutes of Health (NIH) to better understand the epidemiology of Zika virus in pregnancy and the impact the virus has on infant neurodevelopment. [University of North Carolina at Chapel Hill (Newswise, Inc)] Press Release

Neuronascent Awarded $2.25 Million NIH Grant to Develop a Regenerative Therapeutic for Alzheimer’s Disease

Neuronascent Inc. announced that the National Institute on Aging, part of the National Institutes of Health (NIH), has awarded the company an 18-month R01 award. The grant award is expected to total just over $2.25 million and will fund the further development, including Phase I clinical trial of Neuronascent’s lead small molecule therapeutic NNI-362, an oral drug for mild to moderate Alzheimer’s disease. [NeuroNascent, Inc.] Press Release

Amicus Therapeutics Acquires Gene Therapy Portfolio of Ten Clinical and Pre-Clinical Stage AAV Programs in Neurologic Lysosomal Storage Disorders

Amicus Therapeutics announced the signing of a definitive agreement in which Amicus Therapeutics will receive worldwide development and commercial rights for ten gene therapy programs developed at The Center for Gene Therapy at The Research Institute at Nationwide Children’s Hospital and The Ohio State University. [Amicus Therapeutics, Inc.] Press Release

Six Months to Brexit: How Scientists Are Preparing for the Split

The incredible is fast becoming the inevitable. Just six months from now, unless a political earthquake intervenes, the United Kingdom must leave the European Union. Yet the details of the March 2019 break-up are still muddy, and scientists are growing increasingly anxious — and angry — about how Brexit will alter their research and their lives. [Nature News] Editorial

Trump Administration Launches Review of Scientific Research Involving Fetal Tissue

The Trump administration has launched a comprehensive review of all research that involves fetal tissue, reopening an issue that has galvanized anti-abortion activists but worried scientists who fear their work could be under threat. [STAT News] Editorial

NEW 2018 Till & McCulloch Meetings (TMM2018)
November 12-14, 2018
Ottawa, Ontario, Canada

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NEW Tenure Eligible Investigator – Neurobiology (Universite Bourgogne Franche-Comte)

Postdoctoral Research Scientist – Brain Tumors (Columbia University)

PhD Student – Aging and Neurodegeneration (DZNE Deutsches Zentrum für Neurodegenratie Erkrankungen)

Postdoctoral Positions – Neuronal Signaling (Australian National University)

Postdoctoral Research Associate – Cell Biology of Neural Development (St Jude Children’s Research Hospital)

Assistant Professor – Systems Neuroscience (Carnegie Mellon University)

Tenure Eligible Investigator – Neurobiology (Universite Bourgogne Franche-Comté)

Postdoctoral Position – Stem Cell-Based Modeling of Psychiatric Disease (Universitat Bonn)

Excellence in Science PhD Scholarship Award – Neuroscience (University of Technology Sydney)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

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