Neural Cell News Volume 13.40 | Oct 16 2019

TOP STORY

Microglia Drive APOE-Dependent Neurodegeneration in a Tauopathy Mouse Model

Investigators demonstrated that microglia-mediated damage, rather than pathological tau-induced direct neurotoxicity, was the leading force driving neurodegeneration in a tauopathy mouse model. Importantly, the progression of ptau pathology was also driven by microglia. [J Exp Med] Abstract

(Ranked by impact factor of the journal)

Impaired Adult Neurogenesis Is an Early Event in Alzheimer’s Disease Neurodegeneration, Mediated by Intracellular Aβ Oligomers

The authors observed that Tg2576 resident and SVZ-derived adult neural stem cells proliferated significantly less. Further, they failed to terminally differentiate into mature neurons due to pathological, tau-mediated, and microtubule hyperstabilization. [Cell Death Differ] Full Article

TET2 Regulates the Neuroinflammatory Response in Microglia

Researchers showed that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression was increased in microglia upon stimulation with various inflammogens through a NF-κB-dependent pathway. They found that TET2 regulates early gene transcriptional changes, leading to early metabolic alterations, as well as a later inflammatory response independently of its enzymatic activity. [Cell Rep] Full Article | Graphical Abstract

Fast Regulation of GABA_AR Diffusion Dynamics by Nogo-A Signaling

Loss of function for Nogo-A signaling through S1PR2 rapidly increased GABA_AR diffusion, thereby decreasing their number at synaptic sites and the amplitude of GABAergic mIPSCs at CA3 hippocampal neurons. This increase in GABA_AR diffusion rate was correlated with an increase in Ca²⁺ influx and required the calcineurin-mediated dephosphorylation of the γ2 subunit at serine 327. [Cell Rep] Full Article | Graphical Abstract

ACT001, a Novel PAI-1 Inhibitor, Exerts Synergistic Effects in Combination with Cisplatin by Inhibiting PI3K/AKT Pathway in Glioma

Scientists investigated the effects of ACT001 on glioma cell proliferation and clarified its mechanism. They discovered that PAI-1 was the direct target of ACT001 by a cellular thermal shift assay. [Cell Death Dis] Full Article

NPI-0052 and γ-Radiation Induce a Synergistic Apoptotic Effect in Medulloblastoma

Researchers performed an in silico gene expression analysis to evaluate the proteasome subunit expression in medullablastoma (MB). To evaluate the anticancer activity of NPI-0052, they used a range of MB patient-derived MB cells and cell lines. [Cell Death Dis] Full Article

Human Cortical Organoids Expose a Differential Function of GSK3 on Cortical Neurogenesis

Investigators harnessed human cortical brain organoids to probe the longitudinal impact of glycogen synthase kinase 3 (GSK3) inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. [Stem Cell Reports] Full Article | Graphical Abstract

BMP Signaling Mediates Glioma Stem Cell Quiescence and Confers Treatment Resistance in Glioblastoma

The authors that BMP and TGF-β signaling definef divergent molecular and functional identities in glioblastoma, and marked relatively quiescent and proliferative glioma stem cells (GSCs), respectively. Treatment of GSCs with BMP inhibited cell proliferation, but did not abrogate their stem-ness, as measured by self-renewal and tumorigencity. [Sci Rep] Full Article

A Novel 3D Nanofibre Scaffold Conserves the Plasticity of Glioblastoma Stem Cell Invasion by Regulating Galectin-3 and Integrin-β1 Expression

Functionalization with laminin increased the spatial anisotropy of migration and modulates its mode from collective to single cell migration. Mechanistically, equally similar to what has been observed for mesenchymal migration of glioblastoma multiforme in vivo, was the upregulation of galectin-3 and integrin-β1 in Gli4 cells migrating on a nanofiber scaffold. [Sci Rep] Full Article

Transduction Optimization of AAV Vectors for Human Gene Therapy of Glaucoma and Their Reversed Cell Entry Characteristics

Tyrosine double-stranded AAV2 capsid mutants increased transduction in single individual-derived human trabecular meshwork (HTM) cultured cells and all TM-outflow layers of perfused postmortem human eyes. These studies provided the first serotype optimization for gene therapy of glaucoma in humans. [Gene Ther] Full Article

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The Blood-Brain Barrier and Blood-Tumor Barrier in Brain Tumors and Metastases

The authors highlight the cellular and molecular components of the blood-brain barrier (BBB), a specialized neurovascular unit evolved to maintain brain homeostasis. Tumors are known to compromise the integrity of the BBB, resulting in a vasculature known as the blood-tumor barrier (BTB), which is highly heterogeneous and characterized by numerous distinct features, including non-uniform permeability and active efflux of molecules. [Nat Rev Cancer] Abstract

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Hope Biosciences Opens First Phase I/II Stem Cell Trial for Brain Injury Treatment

Hope Biosciences announced that enrollment is now open for a Phase I/II trial evaluating safety and efficacy of Hope Biosciences’ autologous, adipose-derived mesenchymal stem cells for traumatic brain injury and hypoxic-ischemic encephalopathy, in partnership with The University of Texas Health Science Center at Houston. [Hope Biosciences] Press Release

Annexon Biosciences Reports Top-Line Phase Ib Results for Novel C1q Inhibitor ANX007 in Glaucoma

Annexon Bioscience announced encouraging results from a Phase Ib dose-ranging clinical trial to evaluate its anti-C1q antibody, ANX007, in patients with glaucoma. ANX007 is an investigational monoclonal antibody antigen-binding fragment formulated for intravitreal administration. [Annexon Bioscience] Press Release

Holtzman Awarded Watanabe Prize in Translational Research

David Holtzman, MD, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology at Washington University School of Medicine in St. Louis, has received the August M. Watanabe Prize in Translational Research from the Indiana Clinical and Translational Sciences Institute. He was recognized for his work uncovering the causes of Alzheimer’s disease and translating an understanding of its basic biology into potential therapies. [Washington University in St. Louis] Press Release

German Lab Faces Criminal Charges after Undercover Investigation

Charges have been lodged with a state prosecutor after the release of undercover video brought attention to the conditions under which animals are kept at the Laboratory of Pharmacology and Toxicology near Hamburg, The Guardian reported on October 15. [The Scientist] Editorial

Sanger Institute Accused of Misusing African DNA Samples

The Wellcome Sanger Institute in the UK had planned to commercialize a genetics array based on African DNA samples, whistleblowers allege, which would have violated the terms of agreements for using the materials, The Times reports. Two universities in Africa have condemned any commercial endeavors using the samples, some of which came from indigenous tribes. [The Scientist] Editorial

Statistically Speaking, 2019 Nobel Prize Lineup of 11 Men and One Woman Was Bound to Happen

Liselotte Jauffred, a physicist at the University of Copenhagen, wondered about the factors that might be influencing the gender representation in Nobel awards. To find out, Jauffred and two colleagues looked at the data. And they concluded that there’s a 96% likelihood that bias against women, not underrepresentation, accounts for the gender distribution seen in the Nobel Prizes. [ScienceMagazine] Editorial

NEW Translational Cancer Research for Basic Scientists Workshop
November 17-22, 2019
Boston, Massachusetts, United States

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NEW Postdoctoral Fellow – ALS Models (University College London)

Assistant Professor – The Neural Basis of Behavior (Mortimer B. Zuckerman Mind Brain Behavior Institute)

Postdoctoral Scholar – Neural Precursor Cells (University of South Florida)

Faculty Positions – Autism and Neurodevelopmental Disorders (University of South Carolina)

Postdoctoral Researcher – Amyloid Filiments in Neurodegenerative Disease (MRC Laboratory of Molecular Biology)

Assistant/Associate Professor – Pediatric Brain Tumors (Baylor College of Medicine)

Research Fellow – Neurodegenerative Disease (University College London)

Faculty Positions – Brain Disorders (IDG/McGovern Institute for Brain Research)

Postdoctoral Position – Neural Cell Research (New York Medical College)

Postdoctoral Researcher – Neural Research (Flanders Institute for Biotechnology)

Assistant Professor – Neurobiology (University of California, Berkeley)

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