Neural Cell News Volume 10.48 | Dec 7 2016

TOP STORY

Genetic Ablation of AXL Does Not Protect Human Neural Progenitor Cells and Cerebral Organoids from Zika Virus Infection

The AXL protein has been nominated as a key attachment factor for Zika virus (ZIKV) in several cell types including neural progenitor cells (NPCs). However, scientists showed that genetic ablation of AXL has no effect on ZIKV entry or ZIKV-mediated cell death in human induced pluripotent stem cell-derived NPCs or cerebral organoids. These findings call into question the utility of AXL inhibitors for preventing birth defects after infection and suggest that further studies of viral attachment factors in NPCs are needed. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

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Mitochondrial Pyruvate Carrier Regulates Autophagy, Inflammation, and Neurodegeneration in Experimental Models of Parkinson’s Disease

Investigators hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mammalian target of rapamycin activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of Parkinson’s disease. To test this, they used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein–based Caenorhabditis elegans model. [Sci Transl Med] Abstract | Press Release

An NAD⁺-Dependent Transcriptional Program Governs Self-Renewal and Radiation Resistance in Glioblastoma

Researchers reported nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting step in nicotinamide adenine dinucleotide (NAD⁺) synthesis, is highly expressed in glioblastoma tumors and patient-derived glioblastoma stem-like cells. The identification of a NAMPT-E2F2-inhibitor of differentiation axis establishes a link between NAD⁺ metabolism and a self-renewal transcriptional program in glioblastoma. [Proc Natl Acad Sci USA] Abstract | Press Release

Dynamic mRNA Transport and Local Translation in Radial Glial Progenitors of the Developing Brain

The authors developed an ex vivo tissue preparation to mechanically isolate radial glia endfeet from the soma, and used photoconvertible proteins to demonstrate that mRNA is locally translated. Using RNA immunoprecipitation and microarray analyses of endfeet, they discovered FMRP-bound transcripts, which encode signaling and cytoskeletal regulators, including many implicated in autism and neurogenesis. They showed FMRP controls transport and localization of one target, Kif26a. [Curr Biol] Abstract | Press Release | Graphical Abstract

Palmitoylation of Caspase-6 by HIP14 Regulates Its Activation

Caspase-6 (CASP6) has an important role in axonal degeneration during neuronal apoptosis and in the neurodegenerative diseases Alzheimer and Huntington disease. Researchers identified palmitoylation as a novel CASP6 modification and as a key regulator of CASP6 activity. [Cell Death Differ] Abstract

Tenascin-C Orchestrates Glioblastoma Angiogenesis by Modulation of Pro- and Anti-angiogenic Signaling

The authors examined the angiomodulatory role of tenascin-C. They found that direct contact of endothelial cells with tenascin-C disrupts actin polymerization, resulting in cytoplasmic retention of the transcriptional coactivator YAP. Tenascin-C also downregulates YAP pro-angiogenic target genes, thus reducing endothelial cell survival, proliferation, and tubulogenesis. Glioblastoma cells exposed to tenascin-C secrete pro-angiogenic factors that promote endothelial cell survival and tubulogenesis. [Cell Rep] Full Article | Graphical Abstract

Lhx2 Interacts with the NuRD Complex and Regulates Cortical Neuron Subtype Determinants Fezf2 and Sox11

During deep layer neurogenesis, scientists showed that transcription factor Lhx2 binds to distal regulatory elements of Fezf2 and Sox11, critical determinants of neuron subtype identity in the mouse neocortex. They demonstrated that Lhx2 binds to the NuRD histone remodeling complex subunits LSD1, HDAC2, and RBBP4, which are proximal regulators of the epigenetic state of chromatin. Their results provide a mechanistic insight into how Lhx2 acts as a necessary and sufficient regulator of genes that control cortical neuronal subtype identity. [J Neurosci] Abstract

Therapeutic Advantage of Pro-Electrophilic Drugs to Activate the Nrf2/ARE Pathway in Alzheimer’s Disease Models

Alzheimer’s disease is characterized by synaptic and neuronal loss, which occurs at least partially through oxidative stress induced by oligomeric amyloid-β (Aβ)-peptide. Carnosic acid (CA), a chemical found in rosemary and sage, is a pro-electrophilic compound that is converted to its active form by oxidative stress. The authors used both in vitro and in vivo models. For in vitro studies, they evaluated protective effects of CA on primary neurons exposed to oligomeric Aβ. [Cell Death Dis] Full Article

Transcriptional Regulation of Notch1 Expression by Nkx6.1 in Neural Stem/Progenitor Cells during Ventral Spinal Cord Development

Scientists showed transcription factor Nkx6.1 interacts with a cis-element (CR2) and regulates the expression of Notch1 in ventral neural stem/progenitor cell of the developing spinal cord. They showed that the Notch1 expression is modulated by the interaction of Nkx6.1 with a 139 bp enhancer sequence within CR2. Their data reveal a novel mechanism of Notch1 transcriptional regulation in the ventral spinal cord by Nkx6.1 via its binding with Notch1 enhancer CR2 during embryonic development. [Sci Rep] Full Article

Interference with Protease-Activated Receptor 1 Alleviates Neuronal Cell Death Induced by Lipopolysaccharide-Stimulated Microglial Cells through the PI3K/Akt Pathway

Researchers demonstrated that the suppression of PAR-1 leads to down-regulation of inflammatory factors including IL-1β, IL-6, TNF-α, NO, as well as the prevention of activation of NF-κB in BV2 cells. In addition, they found that a PAR-1 antagonist, SCH, prevented LPS-induced excessive microglial activation in a dose-dependent manner. [Sci Rep] Full Article

Functional Diversity of Astrocytes in Neural Circuit Regulation

The authors provide an overview of the regional heterogeneity of neuron–astrocyte interactions indicates novel ways in which they could regulate normal neurological function and shows how they might become dysregulated in disease. [Nat Rev Neurosci] Abstract

Advances in Zika Virus Research: Stem Cell Models, Challenges, and Opportunities

The authors review the remarkable progress in stem cell-based Zika virus research and discuss current challenges and future opportunities. [Cell Stem Cell] Full Article

Emerging Therapies for Inherited Retinal Degeneration

Inherited retinal degenerative diseases, a genetically and phenotypically heterogeneous group of disorders, affect the function of photoreceptor cells and are among the leading causes of blindness. The authors review recent advances in molecular genetics and cell biology are elucidating the pathophysiological mechanisms underlying these disorders and are helping to identify new therapeutic approaches, such as gene therapy, stem cell therapy, and optogenetics. Several of these approaches have entered the clinical phase of development. Artificial replacement of dying photoreceptor cells using retinal prostheses has received regulatory approval. [Sci Transl Med] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

BrainStorm Announces NurOwn^® Data to be Highlighted at the 27^th International Symposium on ALS/MND

BrainStorm Cell Therapeutics Inc. announced data from the company’s Phase II study. NurOwn^® has been administered to approximately 75 patients with ALS in clinical trials conducted in the United States and Israel. In a randomized, double-blind, placebo-controlled clinical trial conducted in the U.S., a clinically meaningful benefit was demonstrated by higher response to NurOwn® compared with placebo. [Press release from BrainStorm Cell Therapeutics Inc. discussing research presented at the 27^th International Symposium on ALS/MND, Dublin] Press Release

Neurimmune and TVM Capital Life Science Announce Creation of AL-S Pharma to Develop Innovative Therapy for Patients with ALS

Neurimmune and TVM Capital Life Science’s latest fund, TVM Life Science Ventures VII, announced their investment in AL-S Pharma AG. AL-S Pharma will develop, to proof-of-concept, AP-101, a human monoclonal antibody targeting misfolded SOD1 for the treatment of amyotrophic lateral sclerosis (ALS) that was generated and pre-clinically validated by Neurimmune’s Reverse Translational Medicine^TM platform. [Neurimmune] Press Release

Einstein and Penn State Researchers Awarded $12.2 Million to Study Alzheimer’s Disease

The National Institutes of Health has awarded researchers at Albert Einstein College of Medicine and Pennsylvania State University a five-year, $12.2 million grant to continue studies on the aging brain, Alzheimer’s disease and other dementias. [Albert Einstein College of Medicine] Press Release

NDSU Researcher Awarded $1.89 Million Grant for Alzheimer’s Study

Jagdish Singh, chair and professor in pharmaceutical sciences in the College of Health Professions at North Dakota State University, is receiving a $1.89 million grant award for an Alzheimer’s disease study. The goal of the research is to develop a new delivery system that uses neurotrophic growth factor to treat and prevent Alzheimer’s disease. The grant from the National Institute on Aging of the National Institutes of Health spans five years. [North Dakota State University] Press Release

ProMIS Neurosciences Announces Novel Alzheimer’s Disease Therapeutic Candidates Block the Neurotoxicity of Prion-Like Forms of Amyloid Beta

ProMIS Neurosciences announced the validated monoclonal antibody therapeutic candidates it is developing for Alzheimer’s disease inhibited the direct neurotoxic effect of prion-like forms of Amyloid beta in vitro. [ProMIS Neurosciences] Press Release

Breakthrough Prize Marks 5^th Anniversary Celebrating Top Achievements in Science and Awards More Than $25 Million in Prizes at Gala Ceremony in Silicon Valley

The Breakthrough Prize and founders Sergey Brin and Anne Wojcicki, Yuri and Julia Milner, and Mark Zuckerberg and Priscilla Chan, announced the recipients of the 2017 Breakthrough Prizes, marking the organization’s fifth anniversary recognizing top achievements in Life Sciences, Fundamental Physics and Mathematics. A combined total of $25 million was awarded at the gala ceremony in Silicon Valley, hosted by Morgan Freeman. Each of the Breakthrough Prizes is worth $3 million, the largest individual monetary prize in science. [Breakthrough Prize] Press Release

Stopgap Spending Bill Leaves US Scientists in Limbo

In what has become a year-end tradition in Washington DC, the US Congress is getting ready to approve a stopgap spending measure before it adjourns for the holidays. Many researchers are more worried about what might come after this temporary funding extension, if it is approved. When president-elect Donald Trump takes office, Republicans will control the White House and both houses of Congress — and their science priorities are very different from those of outgoing President Barack Obama, a Democrat. [Nature News] Editorial

Mexico Proposal to Ban Human-Embryo Research Would Stifle Science

Researchers are waiting to see whether Mexico’s legislature will approve an amendment to the national health law that would ban experiments with human embryos. The amendment is intended to regulate assisted reproduction, including the payment of surrogate mothers, donations to egg and sperm banks and the fertilization of more than three eggs at a time. But it would also ban the creation of human embryos for any purpose except reproduction and any research with existing human embryos. [Nature News] Editorial

CRISPR Heavyweights Battle in US Patent Court

Berkeley and its rival, the Broad Institute of MIT and Harvard in Cambridge, Massachusetts, are each vying for the intellectual property underlying CRISPR–Cas9, which is adapted from a system that bacteria use to fend off viruses. During the hearing the US Patent and Trademark Office judges challenged Berkeley’s central claim: that once its researchers demonstrated that CRISPR–Cas9 could be used to edit DNA in bacteria, any reasonably skilled person could have adapted the technique for use in more complex cells. [Nature News] Editorial

NEW Translational Opportunities in Stem Cell Research
February 27-March 1, 2017
Basel, Switzerland

NEW Synapses and Circuits: Formation, Function and Dysfunction
March 5-8, 2017
Sante Fe, New Mexico, United States

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NEW Postdoctoral Research Scholar – Neurodegenerative Diseases (Buck Insititute)

Post-Doctoral Research Fellow – Neurobiology (Institut of Molecular Biology)

Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Neurobiology of Hunger And Other Homestatic Drivers (Beth Israel Deaconess Medical Center/Harvard Medical School)

Neuroscience Postdoctoral Fellow (Harvard University)

Research Associate Position in Neural Rehabilitation Experiments (Nanyang Technological University)

Postdoctoral Researcher – Alzheimer’s Disease (University of Arkansas)

Computational Biologist – Aging Brain (Columbia University)

NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation)

Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco)

Postdoctoral Fellow – Genetic and Epigenetic Features Parkinson’s and Alzheimer’s Diseases (Van Andel Research Institute)

PhD – Neural Circuits (The International Max Planck Research School for Neural Circuits)

Assistant Professor (Tenure) – Developmental Biology)

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