Neural Cell News Volume 13.11 | Mar 27 2019

TOP STORY

SHANK2 Mutations Associated with Autism Spectrum Disorder Cause Hyperconnectivity of Human Neurons

Researchers generated cortical neurons from induced pluripotent stem cells derived from neurotypic and autism spectrum disorder (ASD)-affected donors. They developed sparse coculture for connectivity assays where SHANK2 and control neurons were differentially labeled and sparsely seeded together on a lawn of unlabeled control neurons. [Nat Neurosci] Abstract

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Soluble TREM2 Ameliorates Pathological Phenotypes by Modulating Microglial Functions in an Alzheimer’s Disease Model

Scientists studied soluable myeloid cells 2 (sTREM2) in the brain of 5xFAD mice, a model of Alzheimer’s disease, by direct stereotaxic injection of recombinant sTREM2 protein or by adeno-associated virus-mediated expression. They found that sTREM2 reduces amyloid plaque load and rescues functional deficits of spatial memory and long-term potentiation. [Nat Commun] Full Article

Altered Serotonergic Circuitry in SSRI-Resistant Major Depressive Disorder Patient-Derived Neurons

The authors studied serotonin (5-HT) biochemistry and observed no significant differences in 5-HT release and reuptake or in genes related to 5-HT biochemistry. SSRI-nonremiters patient-derived serotonergic neurons exhibited altered neurite growth and morphology downstream of lowered expression of key Protocadherin alpha genes as compared to healthy controls and SSRI-nonremiters. [Mol Psychiatry] Abstract

Regorafenib Induces Lethal Autophagy Arrest by Stabilizing PSAT1 in Glioblastoma

Mechanistically, regorafenib directly stabilizes phosphoserine aminotransferase 1 (PSAT1), a critical enzyme for serine synthesis, to trigger PRKAA-dependent autophagy initiation and inhibit RAB11A-mediated autophagosome-lysosome fusion, resulting in lethal autophagy arrest in glioblastoma multiforme (GBM) cells. Maintenance of PSAT1 at a high level is essential for regorafenib-induced GBM suppression. [Autophagy] Abstract

PIP4K2A as a Negative Regulator of PI3K in PTEN-Deficient Glioblastoma

Researchers discovered that PIP4K2A negatively regulates phosphoinositide 3-kinase signaling via p85/p110 component degradation in PTEN-deficient glioblastomas and specifically targets p85 for proteasome-mediated degradation. Overexpression of PIP4K2A suppressed cellular and clonogenic growth in vitro and impeded tumor growth in vivo. [J Exp Med] Full Article

An Increase in Membrane Cholesterol by Graphene Oxide Disrupts Calcium Homeostasis in Primary Astrocytes

Scientists showed that exposure to few-layer graphene/graphene oxide (GO) did not affect cell viability or proliferation. However, proteomic and lipidomic analyses unveiled alterations in several cellular processes, including intracellular Ca²⁺ homeostasis and cholesterol metabolism, which were particularly intense in cells exposed to GO. [Small] Abstract

Cellular Senescence in Progenitor Cells Contributes to Diminished Remyelination Potential in Progressive Multiple Sclerosis

Senescent progenitor cells were identified within demyelinated white matter lesions in progressive MS (PMS) autopsy tissue, and induced pluripotent stem-derived neural progenitor cells (NPCs) from patients with primary PMS (PPMS) were found to express cellular senescence markers compared with age-matched control NPCs. Reversal of this cellular senescence phenotype, by treatment with rapamycin, restored PPMS NPC-mediated support for oligodendrocyte maturation. [Proc Natl Acad Sci USA] Full Article

Targeted Degradation of Aberrant Tau in Frontotemporal Dementia Patient-Derived Neuronal Cell Models

The authors employed targeted protein degradation technology to convert a tau positron emission tomography-probe into a functional degrader of pathogenic tau. The hetero-bifunctional molecule QC-01-175 was designed to engage both tau and Cereblon, a substrate-receptor for the E3-ubiquitin ligase CRL4^CRBN, to trigger tau ubiquitination and proteasomal degradation. [eLife] Abstract

Cell Lines and Immune Classification of Glioblastoma Define Patient’s Prognosis

Scientists worked on two large cohorts of patients suffering from glioblastoma for which clinical data, transcriptomic profiles and outcome were recorded. Transcriptomic profiles of 129 pure glioblastoma cell lines were clustered to generate a glioblastoma cell lines classification. Presence of subtypes of glioblastoma cell lines and immune cells was determined using deconvolution. [Br J Cancer] Full Article

MicroRNA-129 Modulates Neuronal Migration by Targeting Fmr1 in the Developing Mouse Cortex

Researchers found that miR-129-5p and miR-129-3p were expressed in both neural progenitor cells and cortical neurons in the developing murine cortex. Moreover, abnormal miR-129 expression could block radial migration of both the deeper layer and upper layer neurons, and impair the multipolar to bipolar transition. However, antagomir-mediated inhibition resulted in overmigration of neurons. [Cell Death Dis] Full Article

Localization and Dynamic Changes of Neuregulin-1 at C-Type Synaptic Boutons in Association with Motor Neuron Injury and Repair

The authors investigated changes in C-type synaptic boutons after electrical stimulation, pharmacological treatment, and peripheral nerve axotomy. Subsurface cistern-linked neuregulin 1 clusters were severely disrupted in acutely stressed spinal cord motor neurons and after tunicamycin-induced endoplasmic reticulum stress. [FASEB J] Abstract

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Neurological Manifestations of Organic Acidurias

Investigators focus on current knowledge of the organic acidurias, including epidemiology, short-term and long-term neurological and systemic features, diagnosis and prognosis, and recent advances in therapy and pathophysiology. [Nat Rev Neurol] Abstract

Circuit Mechanisms of Parkinson’s Disease

The authors discuss key clinical features of Parkinson’s Disease (PD) and their basis in neural circuit dysfunction. They first review important disease symptoms and some of the responsible neuropathology. They then describe the basal ganglia-thalamocortical circuit, the major locus of PD-related circuit dysfunction, and some of the models that have influenced its study. [Neuron] Full Article

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

MediciNova Announces Upcoming Presentations regarding the SPRINT-MS Phase IIb Trial of MN-166 (Ibudilast) in Progressive Multiple Sclerosis

MediciNova, Inc. announced that additional data from the completed SPRINT-MS Phase IIb trial of MN-166 (ibudilast) in progressive multiple sclerosis will be presented. [Press release from MediciNova, Inc. discussing research to be presented at the 71^st American Academy of Neurology Annual Meeting, Philadelphia] Press Release

Aptinyx to Present Preclinical Data on NYX-458

Aptinyx Inc. announced upcoming presentations highlighting preclinical data on its novel NMDA receptor modulator NYX-458. [Press release from Aptinyx Inc. discussing research to be presented at the 14^th International Conference on Alzheimer’s & Parkinson’s Diseases, Lisbon] Press Release

Imvax to Present Results from Phase Ib Clinical Trial of IGV-001 in Glioblastoma Multiforme

Imvax, Inc. announced that results from the Phase Ib clinical trial of lead product candidate IGV-001 for the treatment of newly diagnosed glioblastoma multiforme will be presented during an oral session in a Clinical Trials Minisymposium. [Press release from Imvax, Inc. (GlobeNewswire, Inc.) discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting 2019, Atlanta] Press Release

Vect-Horus Enters into Collaboration and License Agreement with Ono Pharmaceutical Co., Ltd.

Vect-Horus S.A.S. announced that Vect-Horus and Ono Pharmaceutical Co., Ltd. signed a collaboration and license agreement, focused on the development of novel molecules targeting neurodegenerative diseases. [Vert-Horus] Press Release

Avanir Pharmaceuticals, Inc. Reports Phase III Data Evaluating Investigational AVP-786 for the Treatment of Moderate-to-Severe Agitation in Patients with Alzheimer’s Dementia

Avanir Pharmaceuticals, Inc. announced the results from the first study of the company’s Phase III clinical development program investigating the efficacy, safety and tolerability of deudextromethorphan hydrobromide/quinidine sulfate (AVP-786) for the treatment of moderate-to-severe agitation in patients with Alzheimer’s dementia. [Avanir Pharmaceuticals, Inc.] Press Release

NIH May Bar Peer Reviewers Accused of Sexual Harassment

The National Institutes of Health (NIH) in Bethesda, Maryland, reminded the research community this week that the agency can— and sometimes does— bar scientists accused of sexual harassment from serving as peer reviewers. [ScienceInsider] Editorial

As Elsevier Falters, Wiley Succeeds in Open-Access Deal Making

Over the last few years, Project DEAL, a consortium that represents around 700 academic institutions in Germany, has been in negotiations for nationwide licensing agreements with three of the largest scholarly publishers— Elsevier, Springer Nature, and Wiley. [The Scientist] Editorial

NEW Gordon Research Conference: Neurotrophic Mechanisms in Health & Disease
June 2-7, 2019
Newport, Rhode Island, United States

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

NEW Postdoctoral Fellow – Alcohol & Adult Neurogenesis (The University of Texas at Austin)

NEW Staff Scientist – Development of Mechanism-Based Tumor Therapies (Frankfurt Cancer Institute)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Postdoctoral Research Fellow – Neuroscience (The University of Texas at Austin)

Postdoctoral Researcher – Neurobiology (University of Rochester)

Staff Scientist – Molecular & Behavioral Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

Research Associate – iPSC & Neurodegenerative Disease (TU Dresden)

Researcher Position – Circuit & Behavioral Neuroscience (Instituto Italiano di Tecnologia)

Postdoctoral Position – Neurophysiology (University Medical Center Hamburg Eppendorf)

Postdoctoral Scholar – Brain Tumor Biology (Lund University)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

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