Volume 9.19 | May 20

Neural Cell News 9.19 May 20, 2015
Neural Cell News
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New Mouse Model for ALS and Frontotemporal Dementia Gene Offers Hope for Potential Therapies
Researchers developed a mouse model that exhibits the neuropathological and behavioral features associated with the most common genetic form of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, which are caused by a mutation in the C9ORF72 gene. [Press release from the Mayo Clinic discussing online prepublication in Science] Press Release | Abstract | Video
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PUBLICATIONS (Ranked by impact factor of the journal)
Live Imaging of Adult Neural Stem Cell Behavior in the Intact and Injured Zebrafish Brain
Investigators used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. [Science] Abstract

Presenilin 1 Is Necessary for Neuronal, but Not Glial, EGFR Expression and Neuroprotection via γ-Secretase-Independent Transcriptional Mechanisms
Researchers showed that absence of presenilin 1 (PS1) results in dramatic decrease of neuronal epidermal growth factor receptor (EGFR) and that PS1-null (PS1−/−) brains have reduced amounts of this receptor. PS1−/− cortical neurons contained little EGFR and showed no epidermal growth factor-induced survival signaling or protection against excitotoxicity, but exogenous EGFR rescued both functions even in absence of PS1. [FASEB J] Abstract

E-Cadherin Enhances Neuregulin Signaling and Promotes Schwann Cell Myelination
To determine whether E-cadherin plays a regulatory role during Schwann cell myelination, the authors investigated the effects of E-cadherin deletion and over-expression in Schwann cells. [Glia] Abstract

Oncostatin M-Dependent Mcl-1 Induction Mediated by JAK1/2-STAT1/3 and CREB Contributes to Bioenergetic Improvements and Protective Effects against Mitochondrial Dysfunction in Cortical Neurons
Scientists tested the hypothesis that oncostatin M (OSM) may confer neuronal resistance against 3-nitropropionic acid (3-NP), a plant toxin that irreversibly inhibits the complex II of the mitochondrial electron transport chain, and characterized the underlying molecular mechanisms. They found that OSM preconditioning dose- and time-dependently protected cortical neurons against 3-NP toxicity. [Biochim Biophys Acta] Abstract

Prevention of Human Dopaminergic Neurodegeneration in an Astrocytes Co-Culture System allowing Endogenous Drug Metabolism
Researchers grew an intricate network of human dopaminergic neurons on top of a dense layer of astrocytes. In these co-cultures, 1-methyl-4-phenyl-tetrahydropyridine was metabolized to 1-methyl-4-phenyl-pyridinium by the glial cells, and the toxic metabolite was taken up through the dopamine transporter into neurons. [Br J Pharmacol] Abstract

Psora-4, a Kv1.3 Blocker, Enhances Differentiation and Maturation in Neural Progenitor Cells
A small-molecule selective blocker for Kv1.3, Psora-4, was added to the differentiation medium of cultured mouse neural progenitor cells (NPCs) to assess its effect on NPC differentiation efficiency. [CNS Neurosci Ther] Abstract

Ezh2 Maintains Retinal Progenitor Proliferation, Transcriptional Integrity, and the Timing of Late Differentiation
Scientists showed that during retinal development in mouse, there are dynamic patterns of expression of the polycomb repressive complex 2 catalytic subunit EZH2 in retinal progenitors and some differentiated cells, as well as dynamic changes in the histone modification H3K27me3. [Dev Biol] Abstract

Altered Proliferative Ability of Neuronal Progenitors in PlexinA1 Mutant Mice
Earlier studies have highlighted the importance of neuropilin 1 (Nrp1) and Nrp2 in interneuron migration, therefore scientists assessed the role of PlexinA1 in this process. They observed significantly fewer cells expressing the interneuron markers Gad67 and Lhx6 in the cortex of PlexinA1-/- mice compared to wild-type littermates at E14.5 and E18.5. [J Comp Neurol] Abstract

Plexin-B3 Suppresses Excitatory and Promotes Inhibitory Synapse Formation in Rat Hippocampal Neurons
Researchers demonstrated that Plexin-B2 and Plexin-B3 are present in dendrites, but do not localize in synapses. They found that overexpression of all B-plexins leads to decreased volume of excitatory synapses, and at the same time Plexin-B1 and Plexin-B3 promote inhibitory synapse assembly. [Exp Cell Res] Abstract

Glucagon-Like Peptide-1 Regulates Mitochondrial Biogenesis and Tau Phosphorylation against Advanced Glycation End Product-Induced Neuronal Insult: Studies In Vivo and In Vitro
Investigators demonstrated glucagon-like peptide-1 receptor agonists could inhibit oxidative stress and repair the mitochondrial damage in addition to decreasing tau hyperphosphorylation in PC12 cells treated with advanced glycation end products. [Neuroscience] Abstract

Let7a Involves in Neural Stem Cell Differentiation Relating with TLX Level
The authors investigated whether microRNA-Let7a (Let7a) regulates neural stem cell (NSC) differentiation by targeting the nuclear receptor TLX, which is an essential regulator of NSC self-renewal, proliferation and differentiation. [Biochem Biophys Res Commun] Abstract

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Toward Stem Cell-Based Phenotypic Screens for Neurodegenerative Diseases
Phenotypic screening in neurons and glia derived from patients is now conceivable through unprecedented developments in reprogramming, transdifferentiation, and genome editing. The authors outline progress in this nascent field, but also consider the formidable hurdles to identifying robust, disease-relevant and screenable cellular phenotypes in patient-derived cells. [Nat Rev Neurol] Abstract

Glia Disease and Repair—Remyelination
The authors review the biology of remyelination, including the cells and signals involved; describe when remyelination occurs and when and why it fails and the consequences of its failure; and discuss approaches for therapeutically enhancing remyelination in demyelinating diseases of both children and adults, both by stimulating endogenous oligodendrocyte progenitor cells and by transplanting these cells into demyelinated brain. [Cold Spring Harb Perspect Biol] Abstract

Commonalities in Immune Modulation between Mesenchymal Stem Cells (MSCs) and Neural Stem/Precursor Cells (NPCs)
Increasing evidence suggests that stem cells, other than MSCs, are also capable of immunomodulation. NPCs have been among the first stem cells showing immunomodulatory properties and nowadays represent one the most studied and promising stem cell subtype in still uncurable acute and chronic inflammatory neurological disorders. [Immunol Lett] Abstract

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Agenus Announces Oral Presentation at ASCO Highlighting Improved Survival with Prophage Immunotherapy in Brain Cancer Compared to Historical Controls
Agenus Inc. announced that data on continuing survival from a Phase II study of its Prophage vaccine in glioblastoma multiforme has been selected for an oral presentation. [Press release from Agenus Inc. discussing research to be presented at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago] Press Release

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vTv Therapeutics Initiates Pivotal Phase III Trial Evaluating Azeliragon for the Treatment of Patients with Mild Alzheimer’s Disease
vTv Therapeutics LLC announced enrollment of the first patients into STEADFAST (Single Trial Evaluating Alzheimer’s Disease Following Addition to Symptomatic Therapy), vTv’s Phase III placebo controlled trial of azeliragon, an oral antagonist of the receptor for advanced glycation endproducts for treatment of mild Alzheimer’s disease. [vTv Therapeutics LLC] Press Release

Oncolytics Biotech® Inc. Announces Phase I Study in Pediatric Patients with Brain Tumors
Oncolytics Biotech Inc. announced that following submission to the U.S. Food and Drug Administration for review, the investigational new drug application containing the protocol titled “MC1472: Phase I Study of Replication Competent Reovirus in Combination with GM-CSF in Pediatric Patients with Relapsed or Refractory Brain Tumors” is now active. [Oncolytics Biotech Inc.] Press Release

Alcyone Lifesciences and DNAtrix Enter Clinical Collaboration for Brain Cancer
Alcyone Lifesciences, Inc. and DNAtrix Inc. have entered into an exclusive clinical collaboration. Under the agreement, DNAtrix will utilize Alcyone’s MEMS Cannula targeted delivery platform for the intratumoral delivery of DNX-2401, an oncolytic adenovirus and DNAtrix’s lead product for the treatment of the most aggressive form of brain cancer, glioblastoma. [Alcyone Lifesciences, Inc. (PR Newswire Association LLC)] Press Release

Aphios Granted United States Patent for Alzheimer’s Disease Treatment
Aphios Corporation announced that it was granted United States Patent No. 9,034,347 directed to the treatment of neurodegenerative diseases such as Huntington’s disease, Parkinson’s disease, Down syndrome and Alzheimer’s disease. [Aphios Corporation] Press Release

Denali Therapeutics Launches with Initial Investment to Discover and Develop Treatments for Neurodegenerative Diseases
Denali Therapeutics Inc., a new biotechnology company focused on developing effective therapies for neurodegenerative diseases, announced that it has launched with an initial investment commitment of $217 million. [Denali Therapeutics Inc.] Press Release

Yale Scientist Receives Sanberg Award from American Society of Neural Therapy and Repair
The American Society of Neural Therapy and Repair has awarded the 2015 Bernard Sanberg Memorial Award for Brain Repair to John D. Elsworth, PhD, senior research scientist in psychiatry at Yale School of Medicine. [Yale School of Medicine] Press Release
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NEW The 2015 Alzheimer’s Disease Congress
June 23-25, 2015
London, United Kingdom

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NEW Postdoctoral Fellow Positions – iPSC Research and Banking (University of Magna Graecia)

Research Associate – Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Stem Cell Biology/Neuroscience (Tulane University)

Postdoctoral Fellowships – Neurodevelopment (Vollum Institute)

Postdoctoral Fellow – Neural Tissue Engineering (Nanyang Technological University)

Faculty Positions (IDG/McGovern Institute for Brain Research at Peking University)

PhD Studentship – Neurobiology (Istituto Italiano di Tecnologia)

Postdoctoral Scientist – Neural Stem Cells (Texas Biomedical Research Institute)

Postdoctoral Fellow – Development of the Nervous System and the Origin of Neural Diversity (Columbia University Medical Center)

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