Neural Cell News Volume 11.37 | Sep 20 2017

TOP STORY

Newly ID’d Role of Major Alzheimer’s Gene Suggests Possible Therapeutic Target

Researchers showed that the presence of ApoE4 exacerbates the brain damage caused by toxic tangles of a different Alzheimer’s-associated protein: tau. In the absence of ApoE, tau tangles did very little harm to brain cells. [Press release from the Washington University School of Medicine in St. Louis discussing online prepublication in Nature] Press Release | Abstract | Editorial

(Ranked by impact factor of the journal)

Targeting Neuronal Activity-Regulated Neuroligin-3 Dependency in High-Grade Glioma

Scientists showed that high-grade glioma growth depends on microenvironmental neuroligin-3 (NLGN3), and they identified signaling cascades downstream of NLGN3 binding in glioma and determined a therapeutically targetable mechanism of secretion. Patient-derived orthotopic xenografts of pediatric glioblastoma (GBM), diffuse intrinsic pontine glioma and adult GBM failed to grow in Nlgn3 knockout mice. [Nature] Abstract | Press Release

Nup153 Interacts with Sox2 to Enable Bimodal Gene Regulation and Maintenance of Neural Progenitor Cells

The authors showed that the nucleoporin Nup153 interacts with Sox2 in adult neural progenitor cells, where it is indispensable for their maintenance and controls neuronal differentiation. Genome-wide analyses showed that Nup153 and Sox2 bind and co-regulate hundreds of genes. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

An In Vitro Model of Lissencephaly: Expanding the Role of DCX during Neurogenesis

Researchers established human induced pluripotent stem cells from two males with mutated DCX and classical lissencephaly including smooth brain and abnormal cortical morphology. They showed that neural stem cells, with absent or reduced DCX protein expression, exhibit impaired migration, delay differentiation and cause deficient neurite formation. [Mol Psychiatry] Abstract

Oxytocin Stimulates Hippocampal Neurogenesis via Oxytocin Receptor Expressed in CA3 Pyramidal Neurons

Taking advantage of the conditional knockout mouse model, investigators showed that endogenous oxytocin signaling functions in a non-cell autonomous manner to regulate survival and maturation of newly generated dentate granule cells in adult mouse hippocampus via oxytocin receptors expressed in CA3 pyramidal neurons. [Nat Commun] Full Article

Distinct Roles for Motor Neuron Autophagy Early and Late in the SOD1^G93A Mouse Model of ALS

Using a mouse model of ALS expressing mutant superoxide dismutase 1 (SOD1^G93A), the authors showed that motor neurons form large autophagosomes containing ubiquitinated aggregates early in disease progression. To investigate whether this response is protective or detrimental, they generated mice in which the critical autophagy gene Atg7 was specifically disrupted in motor neurons. [Proc Natl Acad Sci USA] Abstract

Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects Their Survival

Established orthotopic xenograft and syngeneic models of glioblastoma (GBM) were used to determine entry of monoclonal anti-VEGF-A into, and uptake by cells in, the perivascular space. Based on the results, investigators examined CD133⁺ cells derived from GBM tumors in vitro. [Clin Cancer Res] Abstract

Bone Morphogenetic Protein Promotes Lewis X Stage-Specific Embryonic Antigen 1 Expression Thereby Interfering with Neural Precursor and Stem Cell Proliferation

Scientists monitored the expression of the carbohydrate in neonatal and adult neural stem cells and in their progeny. Their results showed that the percentage of immunopositive cells and the levels of LeX-SSEA1 immunoreactivity both increase with postnatal age across all stages of the neural lineage. [Stem Cells] Abstract

Disruption to Schizophrenia-Associated Gene Fez1 in the Hippocampus of HDAC11 Knockout Mice

Loss of histone deacetylase 11 (HDAC11) had no obvious impact on brain morphology and neural stem/precursor cells isolated from Hdac11 knockout mouse/KO mice had comparable proliferation and differentiation characteristics. However, in differentiating neural cells, investigators observed decreased expression of schizophrenia-associated gene fasciculation and elongation protein zeta 1 (Fez1), a gene previously reported to be regulated by HDAC11 activity. [Sci Rep] Full Article

TGF-â1-Induced miR-503 Controls Cell Growth and Apoptosis by Targeting PDCD4 in Glioblastoma Cells

Scientists report that miR-503 is overexpressed in glioblastoma tissue compared with normal human brain tissue. Mechanistically, miR-503 can be induced by TGF-â1 at the transcriptional level by binding the smad2/3 binding elements in the promoter. [Sci Rep] Full Article

PACAP and PAC1R Are Differentially Expressed in Motor Cortex of Amyotrophic Lateral Sclerosis Patients and Support Survival of iPSC-Derived Motor Neurons

Researchers focused their attention on pituitary adenylate cyclase-activating polypeptide (PACAP) and its type 1 receptor (PAC1R), and validated the results of the transcriptome experiments by quantitative reverse transcription-polymerase chain reaction, immunohistochemistry and western blot analysis. [J Cell Physiol] Abstract

Autophagy, Its Mechanisms and Regulation: Implications in Neurodegenerative Diseases

The authors review the pathways of autophagy, its regulation and the possible autophagy-targeting interventions for the treatment of neurodegenerative disorders. [Ageing Res Rev] Abstract

The Heat Shock Response in Neurons and Astroglia and Its Role in Neurodegenerative Diseases

Scientists highlight the complexity of heat shock response activation and address whether neurons and glia sense and respond to protein misfolding and aggregation associated with neurodegenerative diseases, in particular Huntington’s disease and amyotrophic lateral sclerosis, by inducing a pro-survival heat shock response. [Mol Neurodegener] Full Article

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GeNeuro and Servier to Present Six-Month Results from CHANGE-MS Phase IIb Study in Multiple Sclerosis

GeNeuro and Servier announced that six-month data from the CHANGE-MS Phase IIb study will be presented. [Press release from GeNeuro discussing research to be presented at 7^th Joint ECTRIMS-ACTRIMS Meeting (MSParis2017), Paris] Press Release

National Cancer Institute Designates UCLA Brain Cancer Program a Site of Research Excellence

The brain cancer program at University of California, Los Angeles (UCLA)’s Jonsson Comprehensive Cancer Center and the UCLA Brain Tumor Center has been designated a Specialized Program of Research Excellence by the National Cancer Institute, making it one of only five brain cancer programs nationwide to receive this national recognition and substantial research funding. The designation comes with an $11.4 million, five-year grant that recognizes UCLA’s brain cancer program as one of the best in the country. [University of California, Los Angeles] Press Release

New $5.4m Grant Funds JAX Studies of ‘Cognitive Resilience’ to Alzheimer’s Disease

A new five-year grant totaling $5,382,423 to Jackson Laboratory (JAX) Assistant Professor Catherine Kaczorowski will fund research to explore why some people with a family history of Alzheimer’s disease, and even brain changes associated with the disease, nevertheless manage to maintain their cognitive capabilities. [Jackson Laboratory] Press Release

$5 Million Grant Awarded to Arizona-Based Alzheimer’s Research Collaboration

The Banner Alzheimer’s Foundation has been awarded a $5 million grant on behalf of several Arizona-based research institutions to develop an unprecedented public resource of molecular data to help advance the scientific understanding, treatment and prevention of Alzheimer’s disease. [The Translational Genomics Research Institute] Press Release

Dr. Roberta Diaz Brinton Wins Alzheimer’s Drug Discovery Foundation’s Melvin R. Goodes Prize

Roberta Diaz Brinton, PhD, has been named the winner of the 2017 Melvin R. Goodes Prize for Excellence in Alzheimer’s Drug Discovery. The prize, awarded by the Alzheimer’s Drug Discovery Foundation, is the first to recognize researchers developing treatments for Alzheimer’s disease and related dementias. [Alzheimer’s Drug Discovery Foundation] Press Release

HHMI Selects 15 Hanna Gray Fellows to Support Diversity in Science

The Howard Hughes Medical Institute (HHMI) announced the selection of 15 exceptional early career scientists as the first group of HHMI Hanna Gray Fellows. Each fellow will receive up to $1.4 million in funding over eight years, with mentoring and active involvement within the HHMI community. [The Howard Hughes Medical Institute] Press Release | Video

Afraxis Wins NIH Grant to Advance Synaptic Profiling Platform for CNS Drug Discovery

Afraxis Inc. announced that it has won a Small Business Innovation Research Phase I award from the National Institute on Aging to advance its big data phenotypic profiling platform for CNS drug discovery. [Afraxis Inc. (PR Newswire Association LLC.)] Press Release

AgeneBio Receives NIH Grant to Initiate Phase III HOPE4MCI Trial to Treat MCI Due to Alzheimer’s Disease

AgeneBio announced it has been awarded a grant from the National Institute on Aging of the National Institutes of Health (NIH) to support its Phase III HOPE4MCI clinical trial for AGB101. AGB101 is the first and only therapeutic for mild cognitive impairment (MCI) due to Alzheimer’s disease targeting brain network imbalance and potentially the first therapeutic to slow progression to, and delay the onset of, Alzheimer’s dementia. [AgeneBio, Inc.] Press Release

Biohaven and Alzheimer’s Disease Cooperative Study (ADCS) Announce Phase II Clinical Trial Collaboration Evaluating Glutamate Modulating Agent Trigriluzole in Patients with Mild-to-Moderate Alzheimer’s Disease

Biohaven Pharmaceutical Holding Company Ltd. announced its clinical trial collaboration with the ADCS. The ADCS is a leading Alzheimer’s disease clinical trials research consortium that receives major support from the U.S. National Institute on Aging, a part of the US National Institutes of Health. [Biohaven Pharmaceutical Holding Company Ltd.] Press Release

ProMIS Neurosciences Designates PMN330 as Third, Validated Lead Product for Development in Alzheimer’s Disease

ProMIS Neurosciences, Inc. announced it has designated PMN330, a monoclonal antibody targeting toxic prion-like forms of amyloid-beta oligomers, as its third lead product for development in Alzheimer’s disease. [ProMIS Neurosciences, Inc.] Press Release

FDA Approves Amgen and Allergan’s MVASI^™ (Bevacizumab-Awwb) for the Treatment of Five Types of Cancer

Amgen and Allergan plc. announced that the FDA has approved MVASI^™ for all eligible indications of the reference product, Avastin^®. MVASI is the first anti-cancer biosimilar, as well as the first bevacizumab biosimilar, approved by the FDA. [Amgen Inc.] Press Release

Publishers Go after Networking Site for Illicit Sharing of Journal Papers

A major scientific publishing group is taking aim at a social networking site for allowing researchers to illegally post copies of their journal papers. The International Association of Scientific, Technical, and Medical Publishers in Oxford, U.K., and The Hague, the Netherlands, has written to ResearchGate, a networking website for researchers, to express concerns over its article-sharing practices. [ScienceInsider] Editorial

U.S. House Approves 2018 Spending Bills, but Process Far from Finished

The U.S. House of Representatives took a major step toward setting federal science budgets for the 2018 fiscal year. But Congress is still far from the finish line, and final spending levels aren’t likely to be finalized until late this year at the earliest. [ScienceInsider] Editorial

They Got Hundreds of Thousands to Rally. Where Does the March for Science Go from Here?

The hundreds of thousands of people who rallied on the National Mall and in cities worldwide for the March for Science came to be noticed. But as two dozen of them met in New York the following month for a debrief, they faced an obvious reality: A grass-roots organization that was quickly formed to plan a singular event was not, at least immediately, equipped for far-reaching and long-term science advocacy. [STAT News] Editorial

NEW Immunobiology of Primary and Metastatic CNS Cancer: Multidisciplinary Science to Advance Cancer Immunotherapy
February 12-18, 2018
San Diego, California, United States

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NEW PhD Studentships – Molecular Biology (Medical Research Council, Laboratory of Molecular Biology)

Faculty Position – Neurobiology (University of California, Berkeley)

Postdoctoral Positions – Circular RNAs and Circadian Rhythms (Brandeis University)

Postdoctoral Positions – Cancer and/or Glioma Stem Cells (Cornell University)

Faculty Members – Neuroscience (Mercer University)

Postdoctoral Position – Genetic and Viral Causes of Microencephaly (Duke University Medical Center)

Postdoctoral Fellow – Glioblastoma Multiforme (Max Delbrück Center for Molecular Medicine)

Postdoctoral Fellow/Associate Positions – Neuroscience (State University of New York)

Postdoctoral Fellowship Positions and Principal Investigator – Brain Tumors (University of California, San Francisco)

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

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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