Neural Cell News Volume 13.28 | Jul 24 2019

TOP STORY

Multiple Sclerosis Attacks Brain’s ‘Projection Neurons’

Brain damage associated with multiple sclerosis specifically targets a common class of brain cells called projection neurons, according to a new international study by scientists at UC San Francisco, Cambridge University, and the University of Heidelberg. [Press release from University of California San Francisco discussing online prepublication in Nature] Press Release | Abstract | Editorial

(Ranked by impact factor of the journal)

CAR-T Cells Secreting BiTEs Circumvent Antigen Escape without Detectable Toxicity

Investigators developed a bicistronic construct to drive expression of a CAR specific for EGFRvIII, a glioblastoma-specific tumor antigen, and a bispecific T-cell engager (BiTE) against EGFR, an antigen frequently overexpressed in glioblastoma but also expressed in normal tissues. [Nat Biotechnol] Abstract | Editorial

An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma

Researchers found that malignant cells in glioblastoma exist in four main cellular states that recapitulated distinct neural cell types, were influenced by the tumor microenvironment, and exhibited plasticity. The relative frequency of cells in each state varied between glioblastoma samples and was influenced by copy number amplifications of the CDK4, EGFR, and PDGFRA loci and by mutations in the NF1 locus, which each favored a defined state. [Cell] Abstract | Press Release | Graphical Abstract

Nox2 Contributes to Age-Related Oxidative Damage to Neurons and the Cerebral Vasculature

Aging WT brains had high levels of angiotensin II (Ang II) and ROS production; activation of ERK1/2, p53, and γH2AX; and losses of capillaries and neurons. However, these abnormalities were markedly reduced in aging Nox2-knockout brains. [J Clin Invest] Full Article | Graphical Abstract

Activation of Neuronal Genes via LINE-1 Elements upon Global DNA Demethylation in Human Neural Progenitors

Investigators observed that inactivation of DNMT1 in human neural progenitor cells resulted in viable, proliferating cells despite a global loss of DNA CpG-methylation. DNA demethylation led to specific transcriptional activation and chromatin remodeling of evolutionarily young, hominoid-specific LINE-1 elements (L1s), while older L1s and other classes of transposable elements remained silent. [Nat Commun] Full Article | Press Release

Live Cell Imaging Reveals 3′-UTR Dependent mRNA Sorting to Synapses

Researchers used Rgs4 mRNA to investigate 3′-UTR-dependent transport by MS2 live-cell imaging. The majority of observed RNA granules displayed 3′-UTR independent bidirectional transport in dendrites. Importantly, the Rgs4 3′-UTR caused an anterograde transport bias, which required the Staufen2 protein. [Nat Commun] Full Article | Press Release

An Autocrine ActivinB Mechanism Drives TGFβ/Activin Signaling in Group 3 Medulloblastoma

The authors demonstrated that an ActivinB autocrine stimulation was responsible for pathway activation in a subset of Group 3 medulloblastoma (MB) characterized by high PMEPA1 levels. Importantly, galunisertib, a kinase inhibitor of the cognate receptors currently tested in clinical trials for glioblastoma patients, showed efficacy on orthotopically grafted MB-PDX. [EMBO Mol Med] Full Article | Press Release | Graphical Abstract

Exosomes Regulate Neurogenesis and Circuit Assembly

Scientists compared the protein cargo and signaling bioactivity of exosomes released by human induced pluripotent stem cell-derived neural cultures lacking MECP2, a model of the neurodevelopmental disorder Rett syndrome, with exosomes released by isogenic rescue control neural cultures. Quantitative proteomic analysis indicated that control exosomes contained multiple functional signaling networks known to be important for neuronal circuit development. [Proc Natl Acad Sci USA] Full Article | Press Release

PI31 Is an Adaptor Protein for Proteasome Transport in Axons and Required for Synaptic Development

Inactivation of PI31 inhibited proteasome motility in axons and disrupted synaptic proteostasis, structure, and function. Moreover, phosphorylation of PI31 by p38 MAPK enhanced binding to DYNLL1/2 and promoted the directional movement of proteasomes in axons, suggesting a mechanism to regulate loading of proteasomes onto motors. [Dev Cell] Full Article | Graphical Abstract

Proteostasis Is Essential during Cochlear Development for Neuron Survival and Hair Cell Polarity

Researchers showed that altered proteostasis consequent to elongator complex deficiency impacted the proper development of the cochlea and resulted in deafness. In the absence of the catalytic subunit Elp3, differentiating spiral ganglion neurons displayed large aggresome-like structures and underwent apoptosis before birth. [EMBO Rep] Abstract | Graphical Abstract

FMRP Modulates Neural Differentiation through m⁶A-Dependent mRNA Nuclear Export

Fragile X mental retardation 1 (Fmr1) knockout (KO) mice showed delayed neural progenitor cell cycle progression and extended maintenance of proliferating neural progenitors into postnatal stages, phenocopying methyltransferase Mettl14 conditional KO mice that had no N⁶-methyladenosine (m⁶A) modification. [Cell Rep] Full Article | Press Release | Graphical Abstract

Synaptogenesis Stimulates a Proteasome-Mediated Ribosome Reduction in Axons

Scientists observed in vitro that different synaptogenic inducers triggered an overall decrease of ribosomal proteins and rRNA in the axons of spinal motor neurons. They further observed that this process was dependent on the ubiquitin-proteasome system but not on autophagy. [Cell Rep] Full Article | Graphical Abstract

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

Neuroinflammation in Frontotemporal Dementia

The authors discuss specific evidence of neuroinflammatory mechanisms in frontotemporal dementia (FTD) and describe how advances in the understanding of these mechanisms, in FTD as well as in other neurodegenerative diseases, might facilitate the development and implementation of diagnostic tools and disease-modifying treatments for FTD. [Nat Rev Neurol] Abstract

Improving CNS Delivery to Brain Metastases by Blood-Tumor Barrier Disruption

Investigators review blood-brain barrier (BBB) physiology and blood-tumor barrier (BTB) pathophysiology. Additionally, they review the limitations of routinely practiced therapies and three current methods being explored for BBB/BTB disruption for improved delivery of chemotherapy to brain tumors. [Trends Cancer] Abstract

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

Diffusion Pharmaceuticals Reports Favorable Safety Data for Dose-Escalation Run-In of Phase III INTACT Study in Glioblastoma Multiforme Patients

Diffusion Pharmaceuticals Inc. reported that based on favorable safety data in a 19-patient dose-escalation run-in study, the Data Safety Monitoring Board has recommended the continuation of the company’s Phase III clinical trial with trans sodium crocetinate in inoperable glioblastoma multiforme patients. [Diffusion Pharmaceuticals Inc.] Press Release

Orphazyme Completes Enrollment in Phase III Trial Evaluating Arimoclomol in Amyotrophic Lateral Sclerosis

Orphazyme A/S announced that it has completed enrollment in its Phase III trial evaluating arimoclomol for the treatment of Amyotrophic Lateral Sclerosis ahead of schedule. Headline results from the full analysis remain on track for the first half of 2021. [Orphazyme A/S] Press Release

BioXcel Therapeutics Announces BXCL501 Met Primary Endpoint in Phase Ib Placebo-Controlled Trial in the Treatment of Agitation in Patients with Schizophrenia

BioXcel Therapeutics, Inc. announced positive top-line results from the adaptive Phase Ib, randomized, double-blind, placebo-controlled, multi-center, US trial, evaluating multiple doses of BXCL501 for acute treatment of agitation in 135 patients with schizophrenia. [BioXcel Therapeutics, Inc.] Press Release

Kazia to Test GDC-0084 with Radiotherapy in Phase I Clinical Trial at Leading US Cancer Center

Kazia Therapeutics Limited announced that Memorial Sloan Kettering Cancer Center in New York, will investigate the potential use of Kazia’s investigational new drug, GDC-0084, in combination with radiotherapy in a Phase I clinical trial for cancer that has spread to the brain. [Kazia Therapeutics Limited] Press Release

Samus Therapeutics Launches PU-AD Clinical Program in Alzheimer’s Disease

Samus Therapeutics, Inc. announced the initiation of its clinical program for PU-AD, an oral, brain permeable inhibitor of epichaperomes in Alzheimer’s Disease following clearance of its Investigational New Drug application by the FDA. [Samus Therapeutics, Inc.] Press Release

Apic Bio’s APB-102 Receives Orphan Drug Designation from the FDA for the Treatment of Genetic SOD1 ALS

Apic Bio, Inc. announced that the FDA has granted orphan drug designation to APB-102, a gene therapy soon to be in clinical development for the treatment of genetic SOD1 amyotrophic lateral sclerosis. [Apic Bio, Inc. (Business Wire, Inc.)] Press Release

The First 3D Models of Parkinson’s, MS Are Headed into Space

A group of brain organoids are set to blast off to the International Space Station, the first to model Parkinson’s disease and MS in microgravity. A team of researchers from across the country believes the models could shed light on how brain cells behave in these diseases and uncover new approaches to treat them. [FierceBiotech] Press Release

Indonesia’s Strict New Biopiracy Rules Could Stifle International Research

Indonesia’s rich biodiversity and complex geology have lured scientists from abroad for centuries. But a law adopted by Indonesia’s parliament may convince some to go elsewhere. The legislation includes strict requirements on foreign scientists doing research in Indonesia, including the need to recruit local collaborators and a near-ban on exporting specimens, along with stiff sanctions, including jail time, for violators. [ScienceInsider] Editorial

Mexico’s New President Shocks Scientists with Budget Cuts and Disparaging Remarks

A package of harsh austerity measures implemented, has had a deep impact on federally funded laboratories and institutes; it includes a 30% cut to fuel for vehicles and office supplies and a 50% cut to international travel funds and payments to contract workers. Scientists say the cuts are a serious threat to the future of Mexican research. [ScienceInsider] Editorial

NEW 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 Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Tenure-Track Assistant Professor – Cognitive Neuroscience (Lawrene University of Wisconsin)

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)

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 Position – Retinal Stem Cell Biology (Johns Hopkins University)

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.