Neural Cell News Volume 12.50 | Dec 19 2018

TOP STORY

A Tau Homeostasis Signature Is Linked with the Cellular and Regional Vulnerability of Excitatory Neurons to Tau Pathology

Researchers identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons. One of the genes, BCL2-associated athanogene 3 (BAG3), a facilitator of autophagy, was identified as a hub, or master regulator, gene. They verified that reducing BAG3 levels in primary neurons exacerbated pathological tau accumulation, whereas BAG3 overexpression attenuated it. [Nat Neurosci] Abstract | Press Release

(Ranked by impact factor of the journal)

Epigenome-Wide Study Uncovers Large-Scale Changes in Histone Acetylation Driven by Tau Pathology in Aging and Alzheimer’s Human Brains

The authors found that tau overexpression in induced pluripotent stem cell-derived neurons altered chromatin structure and that these effects could be blocked by a small molecule predicted to reverse the tau effect. [Nat Neurosci] Abstract

The DGCR5 Long Noncoding RNA May Regulate Expression of Several Schizophrenia-Related Genes

Using DGCR5 knockdown and overexpression experiments in human neural progenitor cells derived from human induced pluripotent stem cells, scientists identified a potential role for DGCR5 in regulating certain schizophrenia-related genes. [Sci Transl Med] Abstract

Migraine-Associated TRESK Mutations Increase Neuronal Excitability through Alternative Translation Initiation and Inhibition of TREK

Frameshift mutation-induced alternative translation initiation led to the production of a second protein fragment, TRESK-MT2, which co-assembled with and inhibited TREK1 and TREK2, two other two-pore-domain K⁺ channels, to increase trigeminal sensory neuron excitability, leading to a migraine-like phenotype in rodents. [Neuron] Abstract | Editorial | Graphical Abstract

Enhanced Astrocyte Responses Are Driven by a Genetic Risk Allele Associated with Multiple Sclerosis

Researchers investigated the effect of the risk variant, rs7665090^G, located near NFKB1, on astrocytes. The risk variant was associated with increased NF-κB signaling and target gene expression, driving lymphocyte recruitment, in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates and lesion sizes. [Nat Commun] Full Article | Press Release

Transcriptome 3′end Organization by PCF11 Links Alternative Polyadenylation to Formation and Neuronal Differentiation of Neuroblastoma

PCF11 shaped inputs converging on WNT-signaling, and governed cell cycle, proliferation, apoptosis and neurodifferentiation. Postnatal PCF11 down-regulation induced a neurodifferentiation program, and low-level PCF11 in neuroblastoma associated with favorable outcome and spontaneous tumor regression. [Nat Commun] Full Article

D-Aspartate Treatment Attenuates Myelin Damage and Stimulates Myelin Repair

While blocking NMDA or NCX3 significantly prevented D-Aspartate-induced [Ca²⁺]_i oscillations, blocking AMPA and glutamate transporters prevented both the initial and oscillatory [Ca²⁺]_i response as well as D-Aspartate-induced inward currents in oligodendrocyte precursor cells. [EMBO Mol Med] Full Article | Graphical Abstract

Ubiquitination-Independent Repression of PRC1 Targets during Neuronal Fate Restriction in the Developing Mouse Neocortex

Investigators showed that the E3 ubiquitin ligase activity of Ring1B, a core component of polycomb repressive complex 1 (PRC 1), was necessary for the temporary repression of key neuronal genes in neurogenic neural stem or progenitor cells (NPCs) but was dispensable for the persistent repression of these genes associated with the loss of neurogenic potential in astrogliogenic NPCs. [Dev Cell] Abstract | Press Release | Graphical Abstract

Macrophage-Derived IL-1β and TNF-α Regulate Arginine Metabolism in Neuroblastoma

Targeting arginine metabolism, either by blocking cationic amino acid transporter 1-dependent arginine uptake in vitro or therapeutic depletion of arginine by pegylated-recombinant arginase BCT-100, significantly delayed tumor development and prolonged murine survival. [Cancer Res] Abstract

MicroRNA-197 Controls ADAM10 Expression to Mediate MeCP2’s Role in the Differentiation of Neuronal Progenitors

Ectopic expression of methyl-CpG-binding protein 2 (MeCP2) inhibited ADAM10 and thus the NOTCH pathway during neural progenitor cell differentiation. In human cells, this downregulation on ADAM10 was mediated by miRNA-197, which was upregulated by MeCP2. Surprisingly, miR-197 bound to the ADAM10 3′-UTR via its 3′ side, not the canonical seed sequence on the 5′ side. [Cell Death Differ] Full Article

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Myelin Oligodendrocyte Glycoprotein Antibodies in Neurological Disease

The authors provide an overview of the current knowledge of anti-myelin oligodendrocyte glycoprotein (MOG), the metrics of MOG-antibody assays and the clinical associations identified. They collate the data on antibody pathogenicity and the mechanisms that are thought to underlie this. [Nat Rev Neurol] Abstract

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Sunovion and PsychoGenics Announce Positive Results from Pivotal Phase II Study of Novel Investigational Agent SEP-363856 for the Treatment of Schizophrenia

Sunovion Pharmaceuticals Inc. and PsychoGenics Inc. announced that positive results from SEP 361-201, a pivotal Phase II study that evaluated the efficacy and safety of SEP-363856, a novel psychotropic agent for the treatment of patients with schizophrenia, were presented. [Press release from Sunovion Pharmaceuticals Inc. discussing research presented at the 57^th Annual Meeting of the American College of Neuropsychopharmacology (ACNP), Hollywood] Press Release

Alkermes and Biogen Announce Submission of a New Drug Application to U.S. Food and Drug Administration for Diroximel Fumarate in Multiple Sclerosis

Alkermes plc and Biogen Inc. announced that Alkermes has submitted a New Drug Application to the FDA for diroximel fumarate, a novel oral fumarate in development for the treatment of relapsing forms of MS. [Alkermes plc] Press Release

Retrotope Announces First Dosing of RT001 in Patients with Infantile Neuroaxonal Dystrophy (INAD)

Retrotope announced that it has begun enrollment of the first patients and has started dosing of infants with the ultra-rare neurodegenerative disease, INAD. The FDA has granted the company approval to conduct this trial as an open-label Phase II/III clinical trial in 15-20 patients. [Retrotope Inc.] Press Release

FDA Accepts BrainStorm’s NurOwn^® IND Application for Progressive Multiple Sclerosis

BrainStorm Cell Therapeutics Inc. announced that the FDA has accepted the Investigational New Drug (IND) application to initiate a Phase II clinical trial of NurOwn^® for the treatment of progressive MS. [BrainStorm Cell Therapeutics Inc.] Press Release

Ovid Therapeutics Announces Phase Ib/IIa Results of OV935/TAK-935 in Adults with Rare Epilepsies

Ovid Therapeutics Inc. announced results from a 12-week, Phase Ib/IIa clinical trial of OV935/TAK-935 that enrolled 18 adults with rare developmental and epileptic encephalopathies who were not successfully treated with available treatment regimens. [Ovid Therapeutics Inc.] Press Release

Concert Pharmaceuticals Initiates Phase I Clinical Program of CTP-692 for the Treatment of Schizophrenia

Concert Pharmaceuticals, Inc. announced that it has initiated its Phase I clinical program for CTP-692, which is being developed as a novel adjunctive treatment for schizophrenia, a devastating, chronic illness with significant unmet need. [Concert Pharmaceuticals, Inc.] Press Release

BioArctic Outlicenses Its Alpha-Synuclein Antibody Portfolio for Parkinson’s Disease to AbbVie after Receiving Clearance

BioArctic AB announced that BioArctic and its partner AbbVie have received U.S. Federal Trade Commission clearance to license BioArctic’s alpha-synuclein antibody portfolio for Parkinson’s disease and other potential indications to AbbVie. [BioArctic AB] Press Release

Open Science and Data Initiative Announced for Neurofibromatosis

The Children’s Tumor Foundation, together with the Neurofibromatosis Therapeutic Acceleration Program and Sage Bionetworks, has announced the first-ever open data portal for scientific research results in the field of neurofibromatosis. [The Children’s Tumor Foundation] Press Release

Universities ‘Held Hostage’ in Nicaragua’s Political Crisis

The repression has struck particularly hard at Nicaragua’s universities, where firings, arrests, and attacks on students have brought higher education and research to a virtual standstill. “The university system is being held hostage,” says María Luisa Acosta, a human rights lawyer and president of the Nicaraguan Academy of Sciences in Managua. [ScienceInsider] Editorial

Canadian Government Ending Networks of Centres of Excellence Program

Canada’s federal government is ending a 30-year-old research funding program, the Networks of Centres of Excellence, leaving researchers uncertain about where future funding will come from, The Globe and Mail reports. The program will be phased out over the course of the next three years, according to a spokesperson for Science Minister Kirsty Duncan. [The Scientist] Editorial

Plan S: The Ambitious Initiative to End the Reign of Paywalls

Efforts to eradicate paywalls have been gaining stream in Europe. Over the last few years, university consortia in several countries have been pushing for open-access agreements in negotiations that have occasionally led to heated stalemates. [The Scientist] Editorial

Australia Cuts Research Funding for Universities

Australian scientists have expressed disappointment over an AU$328.5 million cut to research funding that had been expected over the next four years. In a budget update, the government announced that it will freeze funding increases for the program that supports research, facilities, and training, including of PhDs, at universities. [Nature News] Editorial

NEW 14^th Annual Biomarkers Congress
February 21-22, 2019
Manchester, United Kingdom

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NEW Associate Professor – Neurophysiology (University of Copenhagen)

Postdoctoral Fellow – Neurotrauma and Neural Repair Mechanisms (University of Pennsylvania)

Assistant/Associate Professor – Neurodevelopmental Disease (Children’s National Health System)

Research Associate – Neuroscience (Cardiff University)

Assistant Professor – Neuroscience (Dalhousie University)

Senior Scientist – Neuroscience Drug Discovery (Ionis Pharmaceuticals)

PhD – Neuroscience (Institute for Neuroscience)

Postdoctoral Associate – Cancer & Stem Cell (Weill Cornell Medicine)

Director – Tanz Centre for Research in Neurodegenerative Diseases (University of Toronto)

Postdoctoral Position – Neuroscience (Boston Children’s Hospital)

Faculty Positions – Translational Neurosciences (Wayne State University)

Postdoctoral Scholar – Medulloblastoma (University of California, San Francisco)

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