Neural Cell News Volume 13.13 | Apr 10 2019

TOP STORY

USP9X Deubiquitinates ALDH1A3 and Maintains Mesenchymal Identity in Glioblastoma Stem Cells

Scientists identified ubiquitin-specific protease 9X (USP9X) as a bona fide deubiquitinase of aldehyde dehydrogenase 1A3 (ALDH1A3) in mesenchymal (MES) glioblastoma stem cells (GSCs). USP9X interacted with, depolyubiquitylated, and stabilized ALDH1A3. Moreover, they showed that FACS-sorted USP9X^hi cells were enriched for MES GSCs with high ALDH1A3 activity and potent tumorigenic capacity. [J Clin Invest] Full Article

(Ranked by impact factor of the journal)

A NOTCH Feed-Forward Loop Drives Reprogramming from Adrenergic to Mesenchymal State in Neuroblastoma

A transcriptional feed-forward circuitry of NOTCH-family transcription factors amplified the NOTCH signaling levels, explaining the swift transition between two semi-stable cellular states. This transition induced genome-wide remodeling of the H3K27ac landscape and a switch from adrenergic super-enhancers (SEs) to mesenchymal (MES) SEs. Once established, the NOTCH feed-forward loop maintained the induced MES state. [Nat Commun] Full Article

Different Soluble Aggregates of Aβ42 Can Give Rise to Cellular Toxicity through Different Mechanisms

The authors found that soluble aggregates formed at different stages of the aggregation process of amyloid beta (Aβ42) induced the disruption of lipid bilayers and an inflammatory response to different extents. They showed that the smaller aggregates were those most potent at inducing membrane permeability and most effectively inhibited by antibodies binding to the C-terminal region of Aβ42. [Nat Commun] Full Article

AUTS2 Isoforms Control Neuronal Differentiation

Scientists report that when neuronal differentiation is initiated, there is a shift in expression from a long isoform to a short AUTS2 isoform. Yeast two-hybrid screen identified the splicing factor SF3B1 as an interactor of both isoforms, whereas the polycomb group proteins, PCGF3 and PCGF5, were found to interact exclusively with the long AUTS2 isoform. [Mol Psychiatry] Abstract

Ultra-Multiplexed Analysis of Single-Cell Dynamics Reveals Logic Rules in Differentiation

Researchers investigated the signaling landscape of neural stem cell differentiation and discovered “cellular logic rules” that revealed the critical role of signal timing and sequence in cell fate decisions. They found synergistic and antagonistic signal interactions and showed that differentiation pathways were highly redundant. [Sci Adv] Full Article | Editorial

LRRK2 Mutations Impair Depolarization-Induced Mitophagy through Inhibition of Mitochondrial Accumulation of RAB10

Defects in leucine rich repeat kinase 2 (LRRK2) mutant patient cells were rescued by LRRK2 knockdown and LRRK2 kinase inhibition. A phosphomimetic RAB10 mutant showed less optineurin interaction and less translocation to depolarized mitochondria than wild-type RAB10, and failed to rescue mitophagy in LRRK2 mutant cells. [Autophagy] Abstract

Chromatin Landscapes Reveal Developmentally Encoded Transcriptional States That Define Human Glioblastoma

Investigators mapped active chromatin landscapes with gene expression, whole exomes, copy number profiles, and DNA methylomes across 44 patient-derived glioblastoma stem cells (GSCs), 50 primary tumors, and 10 neural stem cells to identify essential super-enhancer (SE)-associated genes and the core transcription factors that establish SEs and maintain GSC identity. [J Exp Med] Abstract | Graphical Abstract

REST-DRD2 Mechanism Impacts Glioblastoma Stem Cell-Mediated Tumorigenesis

The authors examined two independent high repressor element-1 silencing transcription factor (REST) glioblastoma stem cell lines using genome-wide assays, biochemical validations, gene knockdown analysis, and mouse tumor models. They analyzed in-house patient tumors and patient data present in The Cancer Genome Atlas. [Neuro Oncol] Abstract

Protection of ZIKV Infection-Induced Neuropathy by Abrogation of Acute Antiviral Response in Human Neural Progenitors

Zika virus (ZIKV) infection directly activated a subset of IFN-stimulated genes in human neuroprogenitors, which depended on the presence of IRF3 and NF-κB rather than IFN production and secretion, highlighting a key role of IFN-independent acute antiviral pathway underlying ZIKV infection-caused neuropathy. [Cell Death Differ] Full Article

Pathogenic Mutations in Neurofibromin Identifies a Leucine-Rich Domain Regulating Glioma Cell Invasiveness

Scientists report that the leucine-rich domain (LRD) of neurofibromin inhibited invasion of human glioblastoma cells without affecting their proliferation. Moreover, under conditions tested, the NF1-LRD failed to hydrolyze Ras-GTP to Ras-GDP, suggesting that its suppressive function is independent of Ras signaling. [Oncogene] Full Article

Subscribe to one of our other 19 science newsletters such as Cancer Stem Cell News & ESC & iPSC News.

Embracing Diversity in the 5-HT Neuronal System

The authors discuss recent data from molecular genetic, genomic and functional methods that, when coupled with classical findings, yield a reframing of the 5-hydroxytryptamine (5-HT) neuronal system as a conglomeration of diverse subsystems with potential to inspire novel, more targeted therapies for clinically distinct 5-HT-related disorders. [Nat Rev Neurosci] Abstract

Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments

Transcriptomic studies are beginning to demonstrate important sex differences and, together with genomic studies, are starting to reveal mechanistic domains of overlap and uniqueness with regards to risk and pathophysiological mechanisms with schizophrenia and bipolar disorder. These studies also implicate GABA and glutamate dysfunction as well as immunologic mechanisms. [Neuron] Full Article

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

INmune Bio Announces Poster Presentation with New Data Regarding Neurodegenerative Disease Drug Candidate, XPro1595

INmune Bio, Inc. announced that Lesley Probert, Ph.D., Head of Immunology Department at the Hellenic Pasteur Institute in Athens, will be presenting a poster about new data on the company’s neurodegenerative disease drug candidate XPro1595. [Press release from INmune Bio, Inc. discussing research presented at the European Conference on Neuroinflammation, London] Press Release

Charles River Laboratories and CHDI Foundation Extend Huntington’s Disease Collaboration

Charles River Laboratories International, Inc. and CHDI Foundation announced a five-year extension of their ongoing collaboration. The organizations began working together in 2005 on drug discovery and development for Huntington’s disease, a genetic neurological disease that causes the progressive dysfunction of nerve cells in the brain. [CHDI Foundation] Press Release

I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical Announce Strategic Collaboration Agreement with Biodextris and a Boston-Based, Leading Academic Medical Center

I-Mab Biopharma and Jiangsu Nhwa Pharmaceutical announced that they have entered into collaborative research agreement with world-renowned scientists and clinicians at the Ann Romney Center for Neurologic Diseases at Brigham and Women’s Hospital and Biodextris to jointly develop a novel immuno-stimulatory therapy for neurologic disorders by harnessing the natural power of the immune system. [I-Mab Biopharma (PR Newswire Association LLC.)] Press Release

Banyan Provides Non-Exclusive License of Traumatic Brain Injury (TBI) Biomarkers to Abbott for Use on Its Core Laboratory Instruments

Banyan announced that it will provide Abbott a license for its TBI blood biomarkers – ubiquitin carboxy-terminal hydrolase-L1 and glial fibrillary acidic protein – for use on Abbott’s core laboratory instruments. [Banyan (Business Wire, Inc.)] Press Release

Samumed Doses First Subject in Phase I Trial of SM07883, a Potential Treatment for Alzheimer’s Disease

Samumed, LLC. announced that it has dosed the first subject in its Phase I trial of SM07883, a potential treatment for Alzheimer’s disease. SM07883 is a novel, oral, small-molecule designed to reduce disease pathology by selectively inhibiting dual-specificity tyrosine phosphorylation-regulated kinase 1A. [Samumed, LLC.] Press Release

Concert Pharmaceuticals Initiates Phase I Multiple-Ascending Dose Trial of CTP-692 as an Adjunctive Treatment for Schizophrenia

Concert Pharmaceuticals, Inc. announced that it has initiated an additional trial in the Phase I program evaluating CTP-692, a novel deuterium-modified form of D-serine being developed as an adjunctive treatment for schizophrenia. The Phase I multiple-ascending dose trial will evaluate the safety, tolerability, and pharmacokinetic profile of CTP-692 in healthy volunteers. [Concert Pharmaceuticals, Inc.] Press Release

Sorrento Therapeutics Announces Discovery of a Potential Non-Dopaminergic Approach to Controling Parkinson’s Motor Symptoms with Resiniferatoxin (RTX) Intrathecal Administration

Sorrento Therapeutics, Inc. announced positive and better than initially hoped for top line results in a discovery study aimed at exploring potential benefits of resiniferatoxin in controling neuro-inflammatory processes associated with Parkinson’s disease in a rodent model. [Sorrento Therapeutics, Inc.] Press Release

uniQure Receives FDA Fast Track Designation for AMT-130 Gene Therapy for the Treatment of Huntington’s Disease

uniQure N.V. announced that the FDA has granted Fast Track designation for AMT-130, the company’s gene therapy candidate for the treatment of Huntington’s disease. AMT-130 comprises a recombinant AAV5 vector carrying a DNA cassette encoding a microRNA that non-selectively lowers or knocks-down human huntingtin protein in Huntington’s disease patients. [uniQure N.V.] Press Release

Kyowa Kirin Announces FDA Acceptance of Istradefylline (KW-6002) New Drug Application Resubmission in the US

Kyowa Hakko Kirin Co., Ltd. announced that the FDA has accepted for review the resubmitted New Drug Application for istradefylline, an investigational selective adenosine A2A receptor antagonist, for use as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease experiencing “OFF” episodes. [Kyowa Hakko Kirin Co., Ltd.] Press Release

SanBio Announces SB623 Regenerative Cell Therapy for Traumatic Brain Injury Has Received Ministry of Health, Labour and Welfare (MHLW) Sakigake Designation

The SanBio Group announced that SB623, a regenerative cell therapy that the group is developing globally for the treatment of chronic motor deficit resulting from traumatic brain injury, has received the Sakigake Designation for innovative medical products from the MHLW of Japan. [SanBio Co,Ltd.] Press Release

Gateway for Cancer Research Approves $1.5 Million Grant to Fund Pediatric Brain Cancer Study at Phoenix Children’s Hospital

Gateway for Cancer Research has approved a $1.5 million grant to help physician scientists at Phoenix Children’s Hospital make progress in combating one of the most devastating, aggressive pediatric brain tumors, called diffuse intrinsic pontine glioma. [Gateway for Cancer Research (PR Newswire Association LLC.)] Press Release

Fellowship to Further International Research Links in Huntington’s Disease

A researcher from the University of Plymouth has been awarded a fellowship from the Royal Society to help tackle neurodegenerative condition, Huntington’s disease. Alongside overseas lead Professor Boun Lu from Fudan University, the UK funding of £111,000 will see the research teams collaborate towards finding a novel treatment strategy for Huntington’s disease. [University of Plymouth (EurekAlert)] Press Release

Racism Rife at Top South African University, Says Report

A damning report that says racism is entrenched at the University of Cape Town has reignited discussions about how to erase the divisive legacy of colonialism at South Africa’s top research institutions. [Nature News] Editorial

FDA, New York Attorney General Go After Stem Cell Clinics

On April 3, the FDA sent letters to 20 companies providing stem cell treatments, reports The New York Times, reminding them that they may require FDA approval and should take action to comply. The agency also issued a warning to a stem cell company for violating good manufacturing practices. [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 Senior Scientist – Tau Biology in Neuroscience Discovery (AbbVie Deutschland GmbH)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

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

Postdoctoral Position – Developmental Neurobiology (University of Liège)

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

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

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)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Neural Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.