Neural Cell News Volume 7.09 | Mar 6 2013

Merlin Isoform 2 in Neurofibromatosis Type 2-Associated Polyneuropathy
Investigators identified a merlin isoform 2-dependent complex that promotes activation of the GTPase RhoA, enabling downstream Rho-associated kinase to promote neurofilament heavy chain phosphorylation. [Nat Neurosci] Abstract

Neuronal ER Stress Impedes Myeloid-Cell-Induced Vascular Regeneration through Inositol-Requiring Enzyme-1α Degradation of Netrin-1
Using the ischemic retina as a model of neurovascular interaction in the CNS, scientists provided evidence that the failure of reparative angiogenesis is temporally and spatially associated with endoplasmic reticulum (ER) stress. [Cell Metab] Abstract | Graphical Abstract

Loss of ALS-Associated TDP-43 in Zebrafish Causes Muscle Degeneration, Vascular Dysfunction, and Reduced Motor Neuron Axon Outgrowth
To determine the physiological function of Tar DNA binding protein of 43 kDa (TDP-43; TARDBP), researchers knocked out zebrafish Tardbp and its paralogue Tardbpl (TAR DNA binding protein-like), which lacks the glycine-rich domain where amyotrophic lateral sclerosis (ALS)- and frontotemporal lobar degeneration with TDP-43⁺ inclusions-associated mutations cluster. [Proc Natl Acad Sci USA]
Abstract | Press Release

Nitration of Hsp90 Induces Cell Death
Scientists showed that nitration of a single tyrosine residue on a small proportion of 90-kDa heat-shock protein (Hsp90), is sufficient to induce motor neuron death by the P2X7 receptor-dependent activation of the Fas pathway. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Neuron-Released Oligomeric α-Synuclein Is an Endogenous Agonist of TLR2 for Paracrine Activation of Microglia
Using a combination of in silico, in vitro and in vivo approaches, investigators showed that extracellular α-synuclein released from neuronal cells is an endogenous agonist for Toll-like receptor 2 (TLR2), which activates inflammatory responses in microglia. [Nat Commun] Abstract

Constitutively Active TrkB Confers an Aggressive Transformed Phenotype to a Neural Crest-Derived Cell Line
Researchers report that in the pheochromocytoma-derived cell line PC12, ΔIgTrkB promoted differentiation by stimulating process outgrowth; however, in the rat neural crest-derived cell line NCM-1, ΔIgTrkB signaling produced a markedly transformed phenotype characterized by increased proliferation, anchorage-independent cell growth, anoikis resistance and matrix invasion. [Oncogene] Abstract

Post Ischemia Intermittent Hypoxia Induces Hippocampal Neurogenesis and Synaptic Alterations and Alleviates Long-Term Memory Impairment
Researchers demonstrated that the maturation of hippocampal neurons is enhanced by postischemia intermittent hypoxia (IH) intervention. The effects of IH intervention in cultured neurons were mediated by increased synaptogenesis, which was primarily regulated by brain-derived neurotrophic factor/PI3K/AKT. [J Cerebr Blood F Met] Abstract

Primary Neuron Culture for Nerve Growth and Axon Guidance Studies in Zebrafish (Danio rerio)
Scientists introduce a robust zebrafish primary neuron culture system for functional nerve growth and guidance assays. Distinct classes of central nervous system neurons from the spinal cord, hindbrain, forebrain, and retina from wild type zebrafish, and fluorescent motor neurons from transgenic reporter zebrafish lines, were dissociated and plated onto various biological and synthetic substrates to optimize conditions for axon outgrowth. [PLoS One] Full Article

Quantitative Imaging of Microtubule Alteration as an Early Marker of Axonal Degeneration after Ischemia in Neurons
Researchers showed that by using the endogenous (label-free) contrast provided by second harmonic generation (SHG) microscopy, it is possible to identify early molecular changes occurring in the microtubules of living neurons under ischemic conditions. This was done by measuring the intensity modulation of the SHG signal as a function of the angular rotation of the incident linearly polarized excitation light. [Biophys J] Abstract

Collapsin Response Mediator Protein 3 Deacetylates Histone H4 to Mediate Nuclear Condensation and Neuronal Death
Scientists found that mouse collapsin response mediator protein 3 (CRMP3) has robust histone H4 deacetylase activity. During excitotoxicity-induced mouse neuronal death, calpain-cleaved, N-terminally truncated CRMP3 undergoes nuclear translocation to cause nuclear condensation through deacetylation of histone H4. [Sci Rep] Full Article

Alzheimer’s Drug Discovery Foundation Awards Grant to Cohbar to Develop a Novel Peptide Therapeutic for Alzheimer’s Disease
The Alzheimer’s Drug Discovery Foundation announced that it has awarded $205,260 in funding to CohBar Inc. to develop a novel mitochondrial peptide for the treatment of Alzheimer’s disease (AD). The peptide has been shown to have neuro-protective effects against a variety of AD-related toxic insults, including amyloid-beta. [CohBar Inc.] Press Release

First Patient Enrolled in Third Phase III Study of Oral Laquinimod for Relapsing-Remitting Multiple Sclerosis
Teva Pharmaceutical Industries Ltd. and Active Biotech announced enrollment of the first patient in the CONCERTO study – the third Phase III placebo-controlled study designed to evaluate the efficacy, safety and tolerability of once-daily oral laquinimod in patients with relapsing-remitting multiple sclerosis. [Teva Pharmaceutical Industries ltd.] Press Release

Probiodrug Sponsoring Symposium to Share Research Findings in the Role of Pyroglutamated Abeta in the Progression of Alzheimer’s Disease
Probiodrug AG announced that it is sponsoring a symposium at the annual AD/PD™ 2013 – The 11th International Conference on Alzheimer’s & Parkinson’s Diseases. During this symposium, Probiodrug and Alzheimer’s disease experts will present evidence elucidating the role of pyroglutamated Abeta in the pathology of Alzheimer’s disease. [Probiodrug AG] Press Release

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

Postdoctoral Position(s) – Cell Biology, Biophysics and Neurobiology (University of Missouri, Kansas City)

Postdoctoral Position – Neuroscience (Children’s Hospital, Harvard Medical School)

Postdoctoral Position – Molecular Pharmacology (Albert Einstein College of Medicine)

Postdoctoral Fellow – Stem Cell Biology (Johns Hopkins School of Medicine)

Postdoctoral Fellow – Neural Stem Cells and Neurogenesis (UT Southwestern Medical Center)

Lecturer or Reader – Associate Professor (University of Reading)

Postdoctoral Position – Adult Neurogenesis and Neural Survival Signaling (University of Kentucky)

Postdoctoral Fellow – Regulation of Gliomagenesis (UT Southwestern Medical Center at Dallas)

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