Neural Cell News Volume 12.45 | Nov 14 2018

TOP STORY

Disease-Specific Oligodendrocyte Lineage Cells Arise in Multiple Sclerosis

The authors performed single-cell transcriptomic analysis of oligodendrocyte (OL) lineage cells from the spinal cord of mice induced with experimental autoimmune encephalomyelitis (EAE), which mimics several aspects of MS. They found unique OLs and OL precursor cells in EAE and uncovered several genes specifically alternatively spliced in these cells. [Nat Med] Abstract | Press Release

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Defective DNA Damage Repair Leads to Frequent Catastrophic Genomic Events in Murine and Human Tumors

Whole-genome sequencing revealed frequent complex genomic rearrangements in brain tumors developing in mice deficient for factors involved in homologous-recombination-repair or non-homologous-end-joining. Catastrophic events were tightly linked to Myc/Mycn amplification, with increased DNA damage and inefficient apoptotic response already observable at early postnatal stages. [Nat Commun] Full Article | Press Release

High-Throughput Three-Dimensional Chemotactic Assays Reveal Steepness-Dependent Complexity in Neuronal Sensation to Molecular Gradients

The authors describe a microfluidic platform that utilized well-controlled 3D diffusion to generate molecular gradients of varied steepness in a large array of hydrogel cylinders, allowing high-throughput 3D chemotactic assays for mechanistic dissection of steepness-dependent neuronal chemotaxis. [Nat Commun] Full Article | Press Release

Excessive Tubulin Polyglutamylation Causes Neurodegeneration and Perturbs Neuronal Transport

Investigators demonstrated that excessive polyglutamylation induced neurodegeneration in a cell‐autonomous manner and could occur in many parts of the central nervous system. Degeneration of selected neurons in CCP1‐deficient mice could be fully rescued by simultaneous knockout of the counteracting polyglutamylase TTLL1. [EMBO J] Abstract | Graphical Abstract

Nitrite Protects Neurons against Hypoxic Damage through S-Nitrosylation of Caspase-6

Researchers found that hypoxia in primary cortical neurons caused neurite retraction, a caspase-6-dependent process. The hypoxic stress activated caspase-6 within the neurite, leading to microtubule disassembly and neurite retraction. [Antioxid Redox Signal] Abstract

The RNA-Binding Protein LIN28 Controls Progenitor and Neuronal Cell Fate during Postnatal Neurogenesis

The RNA-binding protein LIN28 is known to regulate cell fate, tissue growth, and pluripotency; however, a unified understanding of its role at the cellular level has not been achieved. The authors addressed its developmental activity in mammalian postnatal neurogenesis. [FASEB J] Abstract

Nicotine Promotes Neuron Survival and Partially Protects from Parkinson’s Disease by Suppressing SIRT6

Scientists report that nicotine reduced the abundance of SIRT6 in neuronal culture and brain tissue. They found that reduction of SIRT6 was partly responsible for neuroprotection afforded by nicotine. [Acta Neuropathol Commun] Full Article

Brain Injury Induces HIF-1α-Dependent Transcriptional Activation of LRRK2 That Exacerbates Brain Damage

Investigators found that various in vitro and in vivo models of traumatic brain injury markedly enhanced leucine-rich repeat kinase 2 (LRRK2) expression in neurons and also increased the level of hypoxia-inducible factor (HIF)-1α. [Cell Death Dis] Full Article

Lysosomal and Network Alterations in Human Mucopolysaccharidosis Type VII iPSC-Derived Neurons

To identify a neuronal phenotype that could be used to complement genetic analyses, scientists generated two iPSC clones derived from skin fibroblasts of an mucopolysaccharidosis type VII (MPS VII) patient. They found that MPS VII neurons exhibited reduced β-glucuronidase activity and showed previously established disease-associated phenotypes, including glycosaminoglycans accumulation, expanded endocytic compartments, accumulation of lipofuscin granules, more autophagosomes, and altered lysosome function. [Sci Rep] Full Article

The Effect of Rho Kinase Inhibition on Morphological and Electrophysiological Maturity in iPSC-Derived Neurons

Based on the proven association between inhibiting rho kinase (ROCK) and increased neurite complexity, researchers determined if short-term ROCK inhibition during the first 1-2 weeks of differentiation would increase morphological complexity and electrophysiological maturity after several weeks of differentiation. While inhibiting ROCK resulted in increased neurite formation after 24 hours, this effect did not persist at three and six weeks of age. [Cell Tissue Res] Abstract

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Nonsense-Mediated RNA Decay in the Brain: Emerging Modulator of Neural Development and Disease

A selective RNA turnover mechanism that has received recent attention in neurons is nonsense-mediated RNA decay (NMD). NMD has been shown to influence neural development, neural stem cell differentiation decisions, axon guidance and synaptic plasticity. In humans, NMD factor gene mutations cause some forms of intellectual disability and are associated with neurodevelopmental disorders, including schizophrenia and autism spectrum disorder. [Nat Rev Neurosci] Abstract

Multiple Sclerosis

MS is the most common chronic inflammatory, demyelinating and neurodegenerative disease of the central nervous system in young adults. This disorder is a heterogeneous, multifactorial, immune-mediated disease that is influenced by both genetic and environmental factors. [Nat Rev Dis Primers] Abstract

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Novocure Announces More than 70 Presentations on Tumor Treating Fields

Novocure announced that more than 70 presentations on Tumor Treating Fields, including five oral presentations, will be featured. [Press release from Novocure discussing research to be presented at the 23^rd Annual Meeting of the Society for Neuro-Oncology, New Orleans] Press Release

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Ziopharm Oncology Announces Immuno-Oncology Clinical Supply Agreement with Regeneron to Evaluate Combination Therapy for Patients with Brain Cancer

Ziopharm Oncology, Inc. announced a clinical supply agreement with Regeneron Pharmaceuticals, Inc. to evaluate Ziopharm’s Ad-RTS-hIL-12 plus veledimex in combination with Regeneron’s PD-1 antibody Libtayo^® to treat patients with recurrent glioblastoma. [Ziopharm Oncology, Inc.] Press Release

MedDay Pharmaceuticals Announces Full Patient Enrollment for MD1003 Phase III Clinical Trial (SPI2) in Progressive Multiple Sclerosis

MedDay Pharmaceuticals announced full enrollment of SPI2, a Phase III clinical trial designed to confirm the potential of its investigational drug MD1003 in progressive MS as shown in MS-SPI Phase III trial. [MedDay Pharmaceuticals] Press Release

‘Reprogrammed’ Stem Cells Implanted into Patient with Parkinson’s Disease

Japanese neurosurgeons have implanted ‘reprogrammed’ stem cells into the brain of a patient with Parkinson’s disease for the first time. The condition is only the second for which a therapy has been trialled using induced pluripotent stem cells, which are developed by reprogramming the cells of body tissues such as skin so that they revert to an embryonic-like state, from which they can morph into other cell types. [Nature News] Editorial

Drug for Rare Disease Disappoints in Key Trial

A treatment for Niemann-Pick type C, an extremely rare and ultimately fatal neurodegenerative disease, performed no differently than placebo in a pivotal trial in 56 children and youths. [Nature News] Editorial

Bayer’s Regorafenib is the First Drug to Enter GBM AGILE

The Global Coalition for Adaptive Research and Bayer announced today that Bayer’s regorafenib will be the first drug to enter “GBM AGILE” (Glioblastoma Adaptive Global Innovative Learning Environment). GBM AGILE is a revolutionary patient-centered adaptive platform trial that will evaluate multiple therapies for patients with newly diagnosed and recurrent glioblastoma. [The Global Coalition for Adaptive Research (Business Wire Inc.)] Press Release

FDA Grants Orphan Drug Designation to RGX-181 Gene Therapy for the Treatment of CLN2 Form of Batten Disease

REGENXBIO Inc. announced the FDA granted Orphan Drug Designation to RGX-181, a one-time treatment candidate for late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease, one of the most common forms of Batten disease caused by mutations in the tripeptidyl peptidase 1 gene. [REGENXBIO Inc.] Press Release

Research Teams from Salk Institute for Biological Studies, Stanford University, University Hospitals Cleveland Medical Center Selected to Study Healthy Brain Aging, Better Treatments for Neurodegenerative Diseases

The American Heart Association and Allen Institute announced $43 million commitment in research funding for innovative approaches to combat age-related dementia, including Alzheimer’s disease. [Allen Institute] Press Release

With Democrats in Control of U.S. House, Science Panel Gets Fresh Start

The results of divisive midterm elections, with Democrats reclaiming control of the U.S. House of Representatives and Republicans likely strengthening their hold on the Senate, have allowed both parties to claim victory. U.S. scientists are also experiencing mixed emotions. [ScienceInsider] Editorial

In the Palestinian Territories, Science Struggles Against All Odds

Travel restrictions and paltry funding hamper researchers, who are trying to build a scientific base. After decades of conflict, many embittered Palestinians from the occupied territories boycott any form of economic or cultural activities with Israel — including research. But higher education is an exception. [Nature News] Editorial

Africa’s Science ‘Millionaires’: Survey Spotlights Top-Funded Researchers

Africa’s research funding system has created few winners: only 2% or so of scientists from just a handful of countries and fields report receiving million-dollar grants, while almost half say they don’t receive any research funding. [Nature News] Editorial

NEW Keystone Symposia: Windows on the Brain: Formation and Function of Synapses and Circuits and their Disruption in Disease
January 21-25, 2019
Taos, New Mexico, United States

NEW Keystone Symposia: Mammalian Sensory Systems
March 15-19, 2019
Seattle, Washington, United States

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