Neural Cell News Volume 13.26 | Jul 10 2019

TOP STORY

A C19MC-LIN28A-MYCN Oncogenic Circuit Driven by Hijacked Super-Enhancers Is a Distinct Therapeutic Vulnerability in ETMRs: A Lethal Brain Tumor

Scientists investigated Chr19q13.41 miRNA cluster (C19MC) oncogenic mechanisms and discovered a C19MC-LIN28A-MYCN circuit fueled by multiple complex regulatory loops including an MYCN core transcriptional network and super-enhancers resulting from long-range MYCN DNA interactions and C19MC gene fusions. [Cancer Cell] Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

Targeting Neuronal and Glial Cell Types with Synthetic Promoter AAVs in Mice, Non-Human Primates and Humans

Investigators created a library of 230 adeno-associated viruses (AAVs), each with a different synthetic promoter designed using four independent strategies. They showed that a number of these AAVs specifically targeted expression to neuronal and glial cell types in the mouse and non-human primate retina in vivo and in the human retina in vitro. [Nat Neurosci] Abstract

TREM2 Acts Downstream of CD33 in Modulating Microglial Pathology in Alzheimer’s Disease

The authors showed that knockout of CD33 attenuated amyloid beta (Aβ) pathology and improved cognition in 5xFAD mice, both of which were abrogated by additional TREM2 knockout. Knocking out TREM2 in 5xFAD mice exacerbated Aβ pathology and neurodegeneration but reduced Iba1⁺ cell numbers, all of which could not be rescued by additional CD33 knockout. [Neuron] Abstract

Myelinating Schwann Cells Ensheath Multiple Axons in the Absence of E3 Ligase Component Fbxw7

Researchers find that loss of Fbxw7, an E3 ubiquitin ligase component, enhanced the myelinating potential of schwann cells (SCs). Fbxw7 mutant SCs made thicker myelin sheaths and sometimes appeared to myelinate multiple axons in a fashion reminiscent of oligodendrocytes. [Nat Commun] Full Article

Time Series Modeling of Cell Cycle Exit Identifies Brd4 Dependent Regulation of Cerebellar Neurogenesis

Time-series modeling of granule cell progenitor (GCP) cell cycle exit identified downregulation of activity of the epigenetic reader protein Brd4. Brd4 binding to the Gli1 locus was controlled by casein kinase 1δ-dependent phosphorylation during GCP proliferation, and decreased during GCP cell cycle exit. [Nat Commun] Full Article

VPS35 Regulates Tau Phosphorylation and Neuropathology in Tauopathy

The authors showed that overexpression of vacuolar protein sorting 35 (VPS35) led to a reduction of pathological tau in neuronal cells, whereas genetic silencing of VPS35 resulted in its accumulation. Mechanistically the availability of active cathepsin D mediated the effect of VPS35 on pathological tau accumulation. [Mol Psychiatry] Abstract

ANK2 Autism Mutation Targeting Giant Ankyrin-B Promotes Axon Branching and Ectopic Connectivity

Scientists elucidated a mechanism normally limiting axon branching, whereby giant ankyrin-B localized to periodic axonal plasma membrane domains through L1 cell-adhesion molecule protein, where it coupled microtubules to the plasma membrane and prevented microtubule entry into nascent axon branches. [Proc Natl Acad Sci USA] Full Article

Trpc5 Deficiency Causes Hypoprolactinemia and Altered Function of Oscillatory Dopamine Neurons in the Arcuate Nucleus

Researchers identified the canonical transient receptor potential channel Trpc5 as an essential requirement for normal function of dopamine arcuate nucleus (ARC) neurons and prolactin homeostasis. They showed that Trpc5 was required for maintaining highly stereotyped infraslow membrane potential oscillations of dopamine ARC neurons. [Proc Natl Acad Sci USA] Abstract

Agrin-Lrp4-Ror2 Signaling Regulates Adult Hippocampal Neurogenesis in Mice

Low-density lipoprotein receptor-related protein 4 (Lrp4), a receptor for Agrin, was expressed in hippocampal neural stem/progenitor cells (NSPCs) and its mutation blocked basal as well as enriched environment-induced NSPCs proliferation and maturation of newborn neurons. Investigators showed that Lrp4 interacted with and activated receptor tyrosine kinase-like orphan receptor 2 (Ror2); and Ror2 mutation impaired NSPC proliferation. [eLife] Full Article

Stepwise Detection and Evaluation Reveal miR-10b and miR-222 as a Remarkable Prognostic Pair for Glioblastoma

Scientists integrated in vitro experiments on glioblastoma multiforme (GBM) cells and in vivo studies on a mouse model of human glioma to elucidate the synergistic effects between miR-10b and miR-222. Inhibition of miR-10b and miR-222 strongly suppressed GBM cells growth, invasion, and induce apoptosis by co-targeting PTEN and leading to activation of p53 ultimately. [Oncogene] Full Article

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Optical Control of Neuronal Ion Channels and Receptors

The authors discuss the challenges and opportunities of photocontrolling native neuronal signalling pathways, focusing on ion channels and neurotransmitter receptors. They describe existing strategies for rendering receptors and channels light sensitive and provide an overview of the neuroscientific insights gained from such approaches. [Nat Rev Neurosci] Abstract

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

ProMIS Neurosciences to Present Data

ProMIS Neurosciences, Inc. will give an oral presentation on its lead clinical candidate, PMN310 for Alzheimer’s disease. [Press release from ProMIS Neurosciences, Inc. discussing research to be presented at the Annual Alzheimer’s Association International Conference^® (AAIC) 2019, Los Angeles] Press Release

ORYZON to Present Data from ETHERAL Phase IIa Trial

Oryzon Genomics, S.A. announced that the company will present data from the ongoing Phase IIa clinical trial with vafidemstat in Alzheimer’s disease named ETHERAL. [Press release from Oryzon Genomics, S.A. discussing research to be presented at the Annual Alzheimer’s Association International Conference^® (AAIC) 2019, Los Angeles] Press Release

Cortexyme Announces Upcoming Data Presentations

Cortexyme, Inc. announced that its work to pioneer a novel disease-modifying therapeutic approach to treat a key underlying cause of Alzheimer’s and other degenerative diseases will be discussed in two research abstracts. [Press release from Cortexyme, Inc. discussing research to be presented at the Annual Alzheimer’s Association International Conference^® (AAIC) 2019, Los Angeles] Press Release

AIVITA Biomedical Announces New Clinical Data in Ongoing Phase II Brain Cancer Trial

AIVITA Biomedical, Inc. announced new clinical data from its ongoing glioblastoma Phase II clinical trial investigating AIVITA’s platform immunotherapy targeting cancer stem cells. Blood plasma biomarker analyses have identified predictive markers of efficacy in seven of eight treated subjects, a sample that represents 15% of the total clinical trial size. [AIVITA Biomedical, Inc.] Press Release

EIP Pharma Initiates New Study with Neflamapimod for the Treatment of Cognitive Deficits in Patients with Huntington’s Disease

EIP Pharma, Inc. announced the initiation of a new Phase II proof-of-concept study evaluating neflamapimod as a treatment for the cognitive dysfunction associated with Huntington’s disease. [EIP Pharma, Inc. (PR Newswire Association LLC.)] Press Release

ProtoKinetix Reaches Mid-Point of 3^rd Stage of Retinal Cell Replacement Therapy Testing at UBC

ProtoKinetix, Incorporated has reached the mid-point of 3^rd stage of testing in retinal cell replacement therapy at the University of British Columbia (UBC). Functionality testing on experimental models three months post-transplant show encouraging results. [ProtoKinetix, Incorporated] Press Release

Neurogene Initiates Natural History Study of CLN7 and CLN5, Two Forms of Batten Disease

Neurogene Inc. announced it is conducting a natural history study of CLN7 and CLN5, two forms of late-infantile variant Batten disease. The goal of the study is to better understand the course of the disease and to determine clinically meaningful outcome measures for use in future gene therapy trials. [Neurogene Inc.] Press Release

National Institute on Aging Awards $4.23 Million to Establish Cleveland Alzheimer’s Disease Research Center

The National Institute on Aging of the National Institutes of Health awarded a $4.23 million grant to establish the Cleveland Alzheimer’s Disease Research Center. The two-year award will support the development of a multi-institution collaborative focused on accelerating research for Alzheimer’s disease and related dementias. [Cleveland Clinic] Press Release

The Folds in Our Grey Cells

The German Research Foundation has accepted Dr. Silvia Budday into the Emmy Noether program, and has provided her with approximately one million euros in the first funding period to lead a junior research group investigating the mechanics of our brains. [Friedrich-Alexander-Universität] Press Release

Sweden Passes Law For National Research Misconduct Agency

After several high-profile cases, the country’s government is creating a board to oversee and investigate all serious allegations of scientific misconduct. [The Scientist] Editorial

Hungarian Government Takes Control of Research Institutes despite Outcry

After months of struggle between Hungary’s research ministry and its scientific community, the nation’s parliament ratified a law on 2 July that gives the government control over the 40 or so institutes belonging to the Hungarian Academy of Sciences. The government says that its aim is to make research more innovative. [Nature News] Editorial

NEW Society for Neuroscience 2019
October 19-23, 2019
Chicago, Illinois, United States

Visit our events page to see a complete list of events in the community.

NEW Early Stage Researchers – Multiple Sclerosis Research (National University of Ireland Galway)

Postdoctoral Fellowship – Neurogenesis & Neural Cell Aging (Lund University)

Postdoctoral Fellowship – Bioinformatics & Neurogenesis (Lund University)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Research Associate – Cellular & Molecular Neuroscience (University of Cambridge)

Postdoctoral Scientist – Glioma Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Tenure Track Faculty Positions – Neuropharmacology or Neurodegeneration (The University of Tennessee Health Science Center)

Postdoctoral Researcher – Retinal Stem Cell Biology (NIH National Eye Institute)

Postdoctoral Research Fellow – Molecular Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Fellow – Nanoparticle-Based Therapeutic Delivery to the Brain (Johns Hopkins School of Medicine)

Postdoctoral Researcher – Brain Cancer Research (University of Alabama at Birmingham)

Postdoctoral Position – Neuropsychiatric Disorders (Stanford University)

Postdoctoral Fellow – Epigenetic Regulation of Neuronal Identity (The Helmholtz Pioneer Campus)

Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University)

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