Neural Cell News Volume 13.24 | Jun 26 2019

TOP STORY

Frustrated Fish Give Up Thanks to Glia, Not Just Neurons

Until about two decades ago, scientists thought glia just provided support and insulation for neurons. But recent research has begun to uncover new roles for glia in processing. Now, scientists have shown that, in zebrafish, one type of glial cell can calculate when an effort is futile. [Press release from Howard Hughes Medical Institute discussing online prepublication in Cell] Press Release | Full Article | Graphical Abstract

(Ranked by impact factor of the journal)

TREM2 Function Impedes Tau Seeding in Neuritic Plaques

Researchers showed that germline knockout of triggering receptor expressed on myeloid cells 2 (trem2) or the TREM2^R47H variant reduced microgliosis around amyloid-β plaques and facilitated the seeding and spreading of neuritic plaque tau aggregates. [Nat Neurosci] Abstract | Press Release

Deep Sequencing of Somatosensory Neurons Reveals Molecular Determinants of Intrinsic Physiological Properties

The transcriptome profiles of eight dorsal root ganglion (DRG) neuron subtypes revealed differentially expressed and functionally relevant genes, including voltage-gated ion channels. Electrophysiological analyses using pharmacological and genetic manipulations as well as computational modeling of DRG neuron subtypes were undertaken to assess the functions of select voltage-gated potassium channels in shaping action potential waveforms and firing patterns. [Neuron] Abstract

Thrombospondin-1 Mediates Axon Regeneration in Retinal Ganglion Cells

Thrombospondin-1 (THBS1) knockdown in retinal ganglion cells (RGCs) eliminated axon regeneration. Conversely, RGC overexpression of THBS1 enhanced regeneration in both intrinsically photosensitive RGCs (ipRCGs) and non-ipRGCs, an effect that was dependent on syndecan-1, a known THBS1-binding protein. [Neuron] Abstract

Lzts1 Controls Both Neuronal Delamination and Outer Radial Glial-Like Cell Generation during Mammalian Cerebral Development

In neuronally committed cells, Lzts1 functioned in apical delamination by altering apical junctional organization. In apical radial glial cells (aRGs), Lzts1 expression was variable, depending on Hes1 expression levels. According to its differential levels, Lzts1 induced diverse RG behaviors: planar division, oblique divisions of aRGs that generated outer RGs, and their mitotic somal translocation. [Nat Commun] Full Article

Circadian Glucocorticoid Oscillations Preserve a Population of Adult Hippocampal Neural Stem Cells in the Aging Brain

When modeled in primary hippocampal neural stem/precursor cell cultures, glucocorticoid (GC) oscillations controlled cell cycle progression and induced specific genome-wide DNA methylation profiles. GC oscillations induced lasting changes in the methylation state of a group of gene promoters associated with cell cycle regulation and the canonical Wnt signaling pathway. [Mol Psychiatry] Full Article

Myosin IIA Suppresses Glioblastoma Development in a Mechanically Sensitive Manner

Myosin IIA and IIB are the most prevalent isoforms of myosin II in glioblastoma, and the authors showed that codeleting these myosins markedly impaired tumorigenesis and significantly prolonged survival in a rodent model of this disease. However, while targeting just myosin IIA also impaired tumor invasion, it surprisingly increased tumor proliferation in a manner that depended on environmental mechanics. [Proc Natl Acad Sci USA] Abstract

The Interleukin-4/PPARγ Signaling Axis Promotes Oligodendrocyte Differentiation and Remyelination after Brain Injury

Investigators report that interleukin-4 (IL-4) promoted oligodendrocyte regeneration and remyelination. IL-4 receptor expression was detected in a variety of glial cells after ischemic brain injury, including oligodendrocyte lineage cells. IL-4 deficiency in knockout mice resulted in greater deterioration of white matter over 14 days after stroke. [PLoS Biol] Full Article

Spiny and Non-Spiny Parvalbumin-Positive Hippocampal Interneurons Show Different Plastic Properties

Researchers showed that a subset of hippocampal parvalbumin-positive interneurons formed numerous dendritic spines with highly variable densities and input-selective organization. These spines formed in areas with reduced perineuronal net sheathing, predisposed for plastic changes in protein expression, and showed input-specific re-organization after behavioral experience. [Cell Rep] Full Article | Graphical Abstract

Early Seizure Activity Accelerates Depletion of Hippocampal Neural Stem Cells and Impairs Spatial Discrimination in an Alzheimer’s Disease Model

Scientists investigated a transgenic mouse model of Alzheimer’s disease (AD) that exhibited seizures similarly to AD patients and found that neurogenesis was increased in the early stages of disease, as spontaneous seizures became evident, but was decreased below control levels as seizures recurred. [Cell Rep] Abstract | Press Release | Graphical Abstract

Pharmacologic Inhibition of LIMK1 Provides Dendritic Spine Resilience against β-Amyloid

Investigators found that the increased abundance of Rho-associated kinase 1 (ROCK1) in cultured primary rat hippocampal neurons reduced dendritic spine length through a myosin-based pathway, whereas the increased abundance of ROCK2 induced spine loss through the serine and threonine kinase LIMK1. [Sci Signal] Full Article | Press Release

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The Diversity of GABAergic Neurons and Neural Communication Elements

Recent high-throughput single-cell analyses have generated unprecedented data sets characterizing the transcriptomes, morphology and electrophysiology of interneurons. The authors posit that cardinal interneuron types can be defined by their synaptic communication properties, which are encoded in key transcriptional signatures. [Nat Rev Neurosci] Abstract

SILK Studies – Capturing the Turnover of Proteins Linked to Neurodegenerative Diseases

Stable isotope labeling kinetics (SILK) studies offer the potential to elucidate the mechanisms underlying various neurodegenerative disease mechanisms, including neuroinflammation and synaptic dysfunction, and to demonstrate target engagement of novel disease-modifying therapies. [Nat Rev Neurol] Abstract

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C4X Discovery and PhoreMost Collaboration to Accelerate Parkinson’s Disease Drug Discovery Pipeline

C4X Discovery Holdings plc entered into a collaboration with PhoreMost. The collaboration, focused initially in Parkinson’s disease, will combine both company’s technology platforms. [C4X Discovery Holdings plc] Press Release

LineaRx Ships DNA to Support Therapy Development for Neurodegenerative Diseases

LineaRx, Inc. announced that it has shipped multiple customized linear DNA amplicons to Evotec SE to support their research efforts related to neurodegenerative diseases such as Huntington’s, Parkinson’s or Alzheimer’s disease. [LineaRx, Inc. (Business Wire, Inc.)] Press Release

Results of Interim Analysis for Masitinib in Alzheimer’s Disease

AB Science SA reported the outcome from the interim analysis of study AB09004 in Alzheimer’s disease. Study AB09004 is an international, randomized, placebo-controlled, Phase III study evaluating masitinib as a treatment of patients with confirmed mild to moderate Alzheimer’s disease. [AB Science SA] Press Release

Mallinckrodt Achieves 50 Percent Enrollment for Phase IIB Trial Investigating the Use of Acthar^® Gel (Repository Corticotropin Injection) in Amyotrophic Lateral Sclerosis (ALS)

Mallinckrodt plc confirmed it has achieved 50 percent patient enrollment in the company’s Phase IIB study designed to assess the efficacy and safety of Acthar^® gel as an investigational treatment for ALS. [Mallinckrodt plc] Press Release

Enterin’s DEMET Study Enrolls First Patient with Parkinson’s Disease Dementia (PDD)

Enterin Inc. has enrolled the first patient in the DEMET study. The study is an open label multi-center study involving patients with PDD and taking place at 15 US sites. It will enroll 30 patients over a six-month period. [Enterin Inc.] Press Release

AC Immune Reports Initiation of a Phase II Substudy to Increase Understanding of Disease Progression in Familial Alzheimer’s Disease

AC Immune SA announced that Genentech has initiated a substudy in the ongoing Phase II Alzheimer’s Prevention Initiative trial of AC Immune’s investigational candidate, crenezumab. The substudy, which measures tau burden using positron emission tomography, aims to increase the understanding of disease progression in the preclinical stage of autosomal dominantly inherited Alzheimer’s disease. [AC Immune SA] Press Release

Rodin Therapeutics Announces Positive Phase I Results Supporting Continued Development of RDN-929 for Treatment of Neurologic Diseases

Rodin Therapeutics announced positive Phase I results that provide the foundation for continued development of RDN-929, a potent and selective HDAC-CoREST inhibitor designed to increase synaptic density for the treatment of neurologic diseases. [Rodin Therapeutics] Press Release

Ziopharm Oncology Completes Enrollment of Controlled IL-12 Plus Opdivo^® (Nivolumab) Phase I Combination Trial in Brain Cancer

Ziopharm Oncology, Inc. announced completion of enrollment of the third cohort of a Phase I clinical trial evaluating controlled IL-12, in combination with the PD-1 inhibitor OPDIVO^® for the treatment of recurrent or progressive glioblastoma multiforme in adults. [Ziopharm Oncology, Inc.] Press Release

Epygenix Therapeutics Submits Investigational New Drug Application for EPX-100 to the US FDA for the Treatment of Patients with Dravet Syndrome

Epygenix Therapeutics, Inc. announced that the company has submitted Investigational New Drug Application and Fast Track Designation Request for EPX-100 to the FDA for the treatment of patients with Dravet syndrome. Epygenix anticipates that Phase I will be initiated in August 2019. [Epygenix Therapeutics, Inc. (PR Newswire Association LLC.)] Press Release

Bioasis Announces FDA Response to Pre-IND Submission

Bioasis Technologies Inc. announced it had received feedback to its pre-Investigational New Drug (IND) submission to the FDA regarding the planned development of xB3-001, the company’s lead investigational candidate to treat brain cancer. [Bioasis Technologies Inc.] Press Release

Jingsong Zhou Receives $2.88 Million for Novel Research on Lou Gehrig’s Disease

The majority of research on ALS, also known as Lou Gehrig’s disease, focuses on the spinal cord because of how the disease affects neurological function. But Jingsong Zhou is investigating the theory that ALS affects the physiology of the whole body through defective cells in multiple organs. [Universtiy of Texas Arlington] Press Release

USPTO Restarts CRISPR Patent Dispute between Broad and UC

The US Court of Appeals for the Federal Circuit ruled last September that patents held by the Broad Institute of MIT and Harvard University were not in conflict with previously submitted patents from the University of California (UC), Berkeley. But the US Patent and Trademark Office (USPTO) has now posted documents declaring interference between them- meaning they may cover overlapping IP. [The Scientist] Editorial

Iranian Biologists Face US Trial for Trying to Take Proteins Out of the Country

Three Iranian biologists are facing trial in a US court over charges that they violated trade sanctions by attempting to export chemicals known as growth factors, which are commonly used in medical research. The scientists have asked a federal district court judge in Atlanta, Georgia, to dismiss the criminal charges against them. [Nature News] Editorial

NEW Cell Symposia: Hallmarks of Cancer
November 17-19, 2019
Seattle, Washington, United States

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NEW 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)

Associate Professor – Translational Psychiatry (Aarhus University)

Postdoctoral Positions – Neuroscience (Weill Cornell Medical College)

Postdoctoral Fellow – Ion Channel & Neuroscience Research (Johns Hopkins University)

Postdoctoral Fellow/Research Assistant Positions – Glioma Research (NIH National Cancer Institute Laboratory of Pathology)

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

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