Neural Cell News Volume 13.06 | Feb 20 2019

TOP STORY

Cell-of-Origin Susceptibility to Glioblastoma Formation Declines with Neural Lineage Restriction

Researchers systematically assessed the tumor-initiating potential of adult neural populations at various stages of lineage progression. Cell type-specific tamoxifen-inducible Cre recombinase transgenes were used to target glioblastoma-relevant tumor suppressors Nf1, Trp53 and Pten in late-stage neuronal progenitors, neuroblasts and differentiated neurons. [Nat Neurosci] Abstract

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IDH1-R132H Acts as a Tumor Suppressor in Glioma via Epigenetic Up-Regulation of the DNA Damage Response

Using a mouse model and primary patient-derived glioma cultures with isocitrate dehydrogenase 1 (IDH1) mutations, scientists investigated the function of IDH1^R132H in the context of tumor suppressor protein 53 and alpha thalassemia/mental retardation syndrome X-linked gene loss. [Sci Transl Med] Abstract | Press Release

Sphingolipid-Dependent Dscam Sorting Regulates Axon Segregation

Loss- and gain-of-function studies showed that neuronal sphingolipids were critical to prevent aggregation of axonal and dendritic Dscam isoforms, thereby ensuring precise Dscam localization to support axon branch segregation. [Nat Commun] Full Article

Motor Neuron Disease-Associated Loss of Nuclear TDP-43 Is Linked to DNA Double-Strand Break Repair Defects

Transactivation response DNA-binding protein of 43 kDa (TDP-43) was rapidly recruited at double-strand break (DSB) sites to stably interact with DNA damage response and nonhomologous end joining factors, specifically acting as a scaffold for the recruitment of break-sealing XRCC4-DNA ligase 4 complex at DSB sites in induced pluripotent stem cell-derived motor neurons. [Proc Natl Acad Sci USA] Abstract

MAP7D2 Localizes to the Proximal Axon and Locally Promotes Kinesin-1-Mediated Cargo Transport into the Axon

The authors found that MAP7 family member MAP7D2 concentrated at the proximal axon, where it overlapped with the axon initial segment and interacted with kinesin-1. Depletion of MAP7D2 resulted in reduced axonal cargo entry and defects in axon development and neuronal migration. [Cell Rep] Full Article | Graphical Abstract

Autism and Schizophrenia-Associated CYFIP1 Regulates the Balance of Synaptic Excitation and Inhibition

Researchers showed that CYFIP1, and the paralog CYFIP2, were enriched at inhibitory postsynaptic sites. While CYFIP1 or CYFIP2 upregulation increased excitatory synapse number and the frequency of miniature excitatory postsynaptic currents, it had the opposite effect at inhibitory synapses, decreasing their size and the amplitude of miniature inhibitory postsynaptic currents. [Cell Rep] Full Article | Graphical Abstract

Dual Inhibition of GSK3β and CDK5 Protects the Cytoskeleton of Neurons from Neuroinflammatory-Mediated Degeneration In Vitro and In Vivo

Scientists demonstrated that inhibition of CDK5 was involved in, but not sufficient for, neuroprotection. Instead, additional inhibition of GSK3β was required to enhance the neuroprotective effects of CDK5 inhibition, which was confirmed using short hairpin RNA-mediated knockdown of CDK5 and GSK3β. [Stem Cell Reports] Full Article

Glutathione S-Transferases Promote Proinflammatory Astrocyte-Microglia Communication during Brain Inflammation

In astrocytes, glutathione S-transferase M1 was required for the activation of nuclear factor κB and the production of proinflammatory mediators, such as granulocyte-macrophage colony-stimulating factor and C-C motif chemokine ligand 2, both of which enhance microglia activation. [Sci Signal] Abstract

Dexmedetomidine Inhibits Astrocyte Pyroptosis and Subsequently Protects the Brain in In Vitro and In Vivo Models of Sepsis

In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. [Cell Death Dis] Full Article

Microglia as Modulators of Exosomal Alpha-Synuclein Transmission

Exogenous exosomes were found to dysregulate autophagy of the BV2 mouse microglia cell line with presentation of increased accumulation of intracellular alpha-synuclein (α-syn) and accelerated secretion of α-syn into the extracellular space. [Cell Death Dis] Full Article

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Heterogeneity within Classical Cell Types Is the Rule: Lessons from Hippocampal Pyramidal Neurons

Investigators focus on the mounting evidence that the classical CA3, CA1 and subiculum pyramidal cell types all exhibit prominent and spatially patterned within-cell-type heterogeneity, and suggest these cell types provide a model system for exploring the organization and function of such heterogeneity. Given that the hippocampus is structurally simple and evolutionarily ancient, within-cell-type heterogeneity is likely to be a general and crucial feature of the mammalian brain. [Nat Rev Neurosci] Abstract

Therapeutic Landscape for Batten Disease: Current Treatments and Future Prospects

The authors provide an overview of the promising therapeutic avenues for Batten disease, highlighting current FDA-approved clinical trials and prospective future treatments. [Nat Rev Neurol] Abstract

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Lysogene and Sarepta Therapeutics Announce Dosing of the First Patient in AAVance, a Phase II/III Clinical Trial Investigating LYS-SAF302, a Gene Therapy for the Treatment of MPS IIIA (Sanfilippo Syndrome Type A)

Lysogene and Sarepta Therapeutics, Inc. announced that the first patient has been dosed in AAVance, a global Phase II-III clinical trial of LYS-SAF302, a gene therapy for the treatment of Mucopolysaccharidosis Type IIIA (MPS IIIA). [Sarepta Therapeutics] Press Release

AC Immune Announces Anti-tau Monoclonal Antibody Entering Second Phase II Trial in Moderate Alzheimer’s Disease

AC Immune SA announced that Genentech is recruiting patients for a second Phase II trial for an anti-Tau monoclonal antibody, known as MTAU9937A, RO7105705, in moderate Alzheimer’s disease (AD). The same antibody, RG6100, also is being studied by Genentech in a separate Phase II trial to evaluate its efficacy and safety in patients with prodromal-to-mild AD. [AC Immune SA] Press Release

IntelGenx Announces Montreal’s Douglas Mental Health University Institute as Ninth Montelukast VersaFilm™ Phase IIa Clinical Trial Site

IntelGenx Corp. announced that, subject to final research ethics board approval, Montreal’s Douglas Mental Health University Institute has agreed to participate in IntelGenx’s Montelukast VersaFilm™ Phase IIa clinical trial in patients with mild to moderate Alzheimer’s disease. [IntelGenx Corp.] Press Release

Denali Therapeutics Announces First Patient Dosed in Phase IB Study of DNL747 for Alzheimer’s Disease

The study is a 28-day, randomized, double-blind, placebo-controlled crossover design Phase Ib clinical trial in patients with Alzheimer’s disease. Its purpose is to evaluate safety, tolerability, pharmacokinetics, pharmacodynamics, and target and pathway engagement biomarkers in the CSF and blood for oral doses of DNL747. [Denali Therapeutics Inc.] Press Release

National Brain Tumor Society and the Brain Science Foundation Partner to Fund Research for Most Common Brain Tumor Type

National Brain Tumor Society announced a new partnership with the Brain Science Foundation. Under terms of the partnership, the organizations have established the Meningioma Research Fund to raise and grant funds specifically for meningioma research poised to identify and advance treatments aimed at dramatically improving survival and quality of life. [National Brain Tumor Society] Press Release

15 Projects Studying the GBA Gene Receive Nearly $3 Million in Total Funding

The Michael J. Fox Foundation for Parkinson’s Research and The Silverstein Foundation for Parkinson’s with GBA announced nearly $3 million in grants to studies investigating glucocerebrosidase beta acid (GBA). [The Michael J. Fox Foundation for Parkinson’s Research] Press Release

CCAB Announces Creation of New Brain Cancer Therapeutic Company, Empirica Therapeutics, as Part of Its Strategy to Advance New Early-Stage Life Sciences Companies

The Centre for the Commercialization of Antibodies and Biologics (CCAB) announced a license agreement with Empirica Therapeutics Inc. aimed at developing new treatments for one of the deadliest forms of brain cancer, glioblastoma. [The Centre for the Commercialization of Antibodies and Biologics] Press Release

A New Law Was Supposed to Protect South Africans’ Privacy. It May Block Important Research Instead

At a time when giant sample and data repositories called biobanks are transforming health research by allowing multiple researchers to ask different questions of the same data, South Africa’s rule could limit such secondary use of data and hamstring international collaborations. [ScienceInsider] Editorial

Facebook’s Controversies Now Extend to Health and Medicine Issues

The Facebook controversies have come to the world of health and medicine. After last year’s scandals involving Cambridge Analytica and Russian trolls, this time the controversies concern anti-vaccine information and health privacy. [STAT News] Editorial

NEW Keystone Symposia: Cancer Stem Cells – Advances in Biology and Clinical Translation
October 13-17, 2019
Hong Kong, China

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NEW Postdoctoral Positions – Neurodegeneration (Van Andel Research Institute)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Research Fellow – Brain Tumor Biology (University of Bergen)

Postdoctoral Position – Neurobiology (Karolinska Institutet)

Postdoctoral Position – Neurophysiology (University Medical Center Hamburg Eppendorf)

Post Doctoral Scholarship – Brain Tumor Biology (Lund University)

Postdoctoral Scholar – Brain Tumor Biology (Lund University)

Faculty Positions – Developmental Neurosciences (Kent State University)

Postdoctoral Scientist – Regenerative Plasticity of Neural Circuits (Cedars-Sinai Medical Center)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Assistant Member – Developmental Neurobiology (St. Jude Children’s Research Hospital)

Associate Professor/Assistant Professor – Neuroscience (Hong Kong Baptist University)

Postdoctoral Fellowship – Alzheimer’s & Cerebrovascular Disease (Schepens Eye Research Institute/Massachusetts Eye and Eaar)

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