Neural Cell News Volume 11.20 | May 24 2017

TOP STORY

PD-L1 Inhibits Acute and Chronic Pain by Suppressing Nociceptive Neuron Activity via PD-1

Programmed cell death ligand-1 (PD-L1) is typically produced by cancer cells and suppresses immunity through the receptor PD-1 expressed on T cells. However, the role of PD-L1 and PD-1 in regulating pain and neuronal function is unclear. The authors report that both melanoma and normal neural tissues including dorsal root ganglion (DRG) produce PD-L1 that can potently inhibit acute and chronic pain. PD-L1 potently suppressed nociceptive neuron excitability in human DRGs. [Nat Neurosci] Abstract | Press Release

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Sodium Channel Na_V1.9 Mutations Associated with Insensitivity to Pain Dampen Neuronal Excitability

Scientists investigated the effects of a Na_V1.9 mutation (L1302F) and a previously reported mutation (L811P) on neuronal excitability. In transfected heterologous cells, the L1302F mutation caused a large hyperpolarizing shift in the voltage-dependence of activation, leading to substantially enhanced overlap between activation and steady-state inactivation relationships. In transfected small rat dorsal root ganglion neurons, expression of L1302F and L811P evoked large depolarizations of the resting membrane potential and impaired action potential generation. [J Clin Invest] Full Article

KEAP1-Modifying Small Molecule Reveals Muted NRF2 Signaling Responses in Neural Stem Cells from Huntington’s Disease Patients

Researchers characterized a triazole-containing inducer of nuclear factor-erythroid 2 p45-derived factor 2 (NRF2) and elucidated the mechanism by which this molecule activates NRF2 signaling. They used this inducer to probe the functional consequences of selective activation of NRF2 signaling in Huntington’s disease (HD) mouse and human model systems. They discovered a muted NRF2 activation response in human HD neural stem cells, which was restored by genetic correction of the disease-causing mutation. [Proc Natl Acad Sci USA] Abstract | Press Release

Histone Variant H3.3 Orchestrates Neural Stem Cell Differentiation in the Developing Brain

Investigators demonstrated that H3.3 is intrinsically required for neural stem cells (NSCs) proliferation and differentiation. Suppression of the H3.3 mediated by shRNAs caused the reduction of the PAX6-positive NSCs proliferation, and promoted the premature terminal mitosis and neuronal differentiation. [Cell Death Differ] Full Article

A Novel Interaction of PAK4 with PPARγ to Regulate Nox1 and Radiation-Induced Epithelial-to-Mesenchymal Transition in Glioma

Researchers identified grade-dependent p21-activated kinases 4 (PAK4) upregulation in gliomas and determined its role in mesenchymal transition and radioresistance. Ionizing radiation treatment significantly elevated expression and nuclear localization of PAK4 in correlation with induction of reactive oxygen species and mesenchymal transition in glioblastoma cells. [Oncogene] Abstract

Tauroursodeoxycholic Acid Enhances Mitochondrial Biogenesis, Neural Stem Cell Pool, and Early Neurogenesis in Adult Rats

Scientists explored the effects of tauroursodeoxycholic acid (TUDCA) on the regulation of neural stem cell (NSC) fate in neurogenic niches, the subventricular zone (SVZ) of the lateral ventricles and the hippocampal dentate gyrus (DG), using rat postnatal neurospheres and adult rats exposed to the bile acid. TUDCA significantly induced NSC proliferation, self-renewal, and neural differentiation in the SVZ, without affecting DG-derived NSCs. [Mol Neurobiol] Abstract

CDK5-Mediated Phosphorylation-Dependent Ubiquitination and Degradation of E3 Ubiquitin Ligases GP78 Accelerates Neuronal Death in Parkinson’s Disease

Investigators addressed the relationship between cyclin-dependent kinase 5 (CDK5) and E3 ubiquitin ligase glycoprotein 78 (GP78) in MPTP-based Parkinson’s disease (PD) models. They found that GP78 expression was decreased in MPTP-based cellular and animal PD models, and CDK5 directly phosphorylated GP78 at Ser516, which promoted the ubiquitination and degradation of GP78. [Mol Neurobiol] Abstract

Induction of Senescence in Primary Glioblastoma Cells by Serum and TGFβ

Researchers exposed PriGO8A primary glioblastoma cells to media with 10% serum and induced a senescence-like phenotype characterized by increased senescence-associated β galactosidase activity, PML bodies and p21 and morphological changes typical of senescence. Microarray expression analysis showed that 24 hour serum exposure increased the expression of genes associated with the TGFβ pathway. [Sci Rep] Full Article

EndophilinAs Regulate Endosomal Sorting of BDNF-TrkB to Mediate Survival Signaling in Hippocampal Neurons

The authors discovered a novel role of EndophilinAs in the sorting of activated BDNF-TrkB receptors into late endosomal compartments. In response to BDNF, EndophilinA2 was recruited to both early and late endosomes, EndophilinA3 was recruited to Lamp1-positive late endosomes, and co-trafficked with Rab5 and Rab7 in both the presence and absence of BDNF, while EndophilinA1 colocalized at lower levels with endosomes. The absence of all three EndophilinAs caused TrkB to accumulate in EEA1 and Rab7-positive endosomes, and impaired BDNF-TrkB-dependent survival signaling cascades. [Sci Rep] Full Article

The Kv1-Associated Molecules TAG-1 and Caspr2 Are Selectively Targeted to Axon Initial Segment in Hippocampal Neurons

Scientists showed that TAG-1 strongly co-localizes with Kv1.2 at the axon initial segment of cultured hippocampal neurons whereas Caspr2 is uniformly expressed along the axolemma. Live-cell imaging revealed that Caspr2 and TAG-1 are sorted together in axonal transport vesicles. Using deletion constructs, they identified two molecular determinants of Caspr2 regulating its axonal positioning. [J Cell Sci] Abstract

Cerebral Blood Flow Regulation and Neurovascular Dysfunction in Alzheimer Disease

The authors examine the cellular and molecular mechanisms within the neurovascular unit that contribute to cerebral blood flow control, and neurovascular dysfunction in neurodegenerative disorders such as Alzheimer disease. [Nat Rev Neurosci] Abstract

Modulators of Microglial Activation and Polarization after Intracerebral Hemorrhage

Researchers summarize key studies on modulators of microglial activation and polarization after intracerebral hemorrhage, including M1-like and M2-like microglial phenotype markers, transcription factors and key signaling pathways. [Nat Rev Neurol] Abstract

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MT Pharma America Presents 12-Month RADICAVA™ (Edaravone) and Amyotrophic Lateral Sclerosis Data

MT Pharma America, Inc. presented open-label extension data that showed patients with amyotrophic lateral sclerosis (ALS) treated with RADICAVA™ for 48 weeks experienced significantly less decline in physical function, as measured by the ALS Functional Rating Scale-Revised, compared with patients given placebo for six months followed by six months of RADICAVA™. [Press release from MT Pharma America, Inc. discussing research presented at the 2017 European Network for the Cure of ALS (ENCALS) annual meeting, Ljubljana, Slovenia] Press Release

Penn Researchers Receive $9.25M Grant from the Paul G. Allen Family Foundation to Study Cellular Mechanisms of Concussion and Ways to Improve Recovery

The Paul G. Allen Family Foundation announced it has awarded a $9.25 million grant to Penn researchers to study the underlying mechanisms of concussion and help uncover potential clinical interventions that could improve recovery. [Penn Medicine] Press Release

BrainStorm Initiated Technology Transfer to City of Hope for U.S. Production of NurOwn^® for Phase III ALS Study

BrainStorm Cell Therapeutics Inc. announced that it has begun training the cell manufacturing team at City of Hope’s Center for Biomedicine and Genetics to produce clinical supplies of NurOwn^® adult stem cells for the company’s randomized, double-blind, multi-dose Phase III clinical study in patients with amyotrophic lateral sclerosis (ALS). [BrainStorm Cell Therapeutics Inc.] Press Release

Celgene Announces Positive Results from RADIANCE, the Second Pivotal Phase III Trial of Oral Ozanimod in Patients with Relapsing Multiple Sclerosis

Celgene Corporation announced that its Phase III RADIANCE trial, evaluating the efficacy and safety of ozanimod, an investigational oral, selective S1P 1 and 5 receptor modulator, in patients with relapsing multiple sclerosis, met the primary endpoint in reducing annualized relapse rate, compared to weekly interferon β-1a. [Celgene Corporation] Press Release

ProMIS Neurosciences Designates PMN350 Its Second Lead Product for Development in Alzheimer’s Disease

ProMIS Neurosciences announced that it has designated PMN350 – a monoclonal antibody targeting toxic prion-like forms of amyloid-beta oligomers – as the company’s second lead product for Alzheimer’s disease. [ProMIS Neurosciences, Inc.] Press Release

NeuroVive to Continue NeuroSTAT^® Clinical Development after Positive Outcome in Preclinical and Clinical TBI Studies

The combined positive outcome of the results from the clinical Phase IIa Copenhagen Head Injury Cyclosporine (CHIC) study and the preclinical studies, done in collaboration with the University of Pennsylvania, USA, have now convinced NeuroVive to proceed into the next stage of clinical development. The company therefore decided to close the CHIC study in advance and focus its traumatic brain injury (TBI) project efforts on preparing for the next clinical study with NeuroSTAT for TBI. [NeuroVive Pharmaceutical AB] Press Release

Herantis Pharma Granted a U.S. Patent on Therapeutic Use of MANF

The United States (U.S.) Patent and Trademark Office has issued to Herantis Pharma Plc a patent titled “Neurotrophic factor MANF and uses thereof“. The patent is for the use of mesencephalic astrocyte-derived neurotrophic factor (MANF) for the treatment of neurological diseases including Parkinson’s disease, epilepsy, and ischemic brain injury. [Herantis Pharma Plc] Press Release

Academies Calculate How Much Brexit Will Cost U.K. Researchers

Some academic fields in the United Kingdom (U.K.) will have major funding holes to fill once the country leaves the European Union, according to new research commissioned by four U.K. academies. [ScienceInsider] Editorial

What’s in Trump’s 2018 Budget Request for Science?

President Donald Trump unveiled his full 2018 budget request to Congress. The spending plan, for the fiscal year that begins 1 October, fleshes out the so-called skinny budget that the White House released this past March. That plan called for deep cuts to numerous research agencies. [ScienceInsider] Editorial

NEW 2017 Acute Stroke Care Symposium
June 24, 2017
Houston, United States

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NEW Postdoctoral Scientist – Neural Stem Cell Biology (Institute for Neuroscience of Montpellier)

NEW Postdoctoral Research Fellow – Brain Neural Networks (Melbourne University)

NEW Faculty Position(s) – Pain Medicine (Southern University of Science and Technology)

Senior/Principle Research Associate – Cell and Molecular Biology (Editas Medicine)

Postdoctoral Fellow – Neuroendocrine Biology of Metabolism (The Scripps Research Institute)

Research Fellow – Neuroscience and Behavioral Disorders (Duke-NUS Medical School)

Postdoctoral Scientist – Cell Biology (Medical Research Council)

Postdoctoral Position – Molecular Biology (KU Leuven)

Postdoctoral Researcher – Neuroscience and Imaging (Howard Hughes Medical Institute)

Director – BrainHub (Carnegie Mellon University)

Postdoctoral Position(s) – Visual Neuroscience (Yale University)

Postdoctoral Fellow – Spinal Cord Injury Repair (Burke Medical Research Institute Cornell)

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

Postdoctoral Positions – Stem Cell Technology/Neuroscience/Drug Discovery (University of California Davis)

Neuroscientist – Precision Neurotherapeutics (University of California Davis)

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