Neural Cell News Volume 11.36 | Sep 13 2017

TOP STORY

Scientists Discover Key Cellular Mechanism Underlying Parkinson’s Disease

Scientists have identified a toxic cascade that leads to neuronal degeneration in patients with Parkinson’s disease (PD). They showed how interventions early in the disease process may be able to break the pathogenic cycle and improve neuronal function in PD. [Press release from Northwestern University discussing online prepublication in Science] Press Release | Abstract

(Ranked by impact factor of the journal)

Identification of GPC2 as an Oncoprotein and Candidate Immunotherapeutic Target in High-Risk Neuroblastoma

Researchers developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. They showed that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. [Cancer Cell] Abstract | Press Release | Graphical Abstract

MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts

Scientists showed that the brain-enriched miRNAs miR-9/9* and miR-124 (miR-9/9*-124) trigger reconfiguration of chromatin accessibility, DNA methylation, and mRNA expression to induce a default neuronal state. miR-9/9*-124-induced neurons were functionally excitable and uncommitted toward specific subtypes but possessed open chromatin at neuronal subtype-specific loci. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

Glia-Specific Enhancers and Chromatin Structure Regulate NFIA Expression and Glioma Tumorigenesis

By examining the regulation of the transcription factor NFIA in the developing spinal cord, investigators identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9–Brn2 and Isl1–Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations. [Nat Neurosci] Abstract | Press Release

Zfp423/ZNF423 Regulates Cell Cycle Progression, the Mode of Cell Division and the DNA Damage Response in Purkinje Neuron Progenitors

To characterize the function of ZNF423 in neurogenesis in vivo, scientists analyzed allelic murine mutants in which distinct functional domains are deleted. One deletion impaired mitotic spindle orientation, leading to premature cell cycle exit and Purkinje cell progenitor pool deletion. [Development] Abstract

LRRK2 Functions as a Scaffolding Kinase of ASK1-Mediated Neuronal Cell Death

Researchers showed that leucine-rich repeat kinase 2 (LRRK2) played an important role in neuronal cell death by directly phosphorylating and activating apoptosis signal-regulating kinase 1 (ASK1). LRRK2 phosphorylated ASK1 at Thr832 that was adjacent to Thr845, which served as an autophosphorylation site. [Biochim Biophys Acta] Abstract

Induced Pluripotent Stem Cell-Derived Neural Stem Cell Therapy Enhances Recovery in an Ischemic Stroke Pig Model

Investigators showed that induced pluripotent stem cell-derived neural stem cell (iNSC) transplantation improves recovery through neuroprotective, regenerative, and cell replacement mechanisms in a novel ischemic pig stroke model. iNSCs differentiated into neurons and oligodendrocytes with indication of long term integration. [Sci Rep] Full Article

Neuroblastoma Patient-Derived Xenograft Cells Cultured in Stem-Cell Promoting Medium Retain Tumorigenic and Metastatic Capacities but Differentiate in Serum

The authors showed that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities. [Sci Rep] Full Article

Transplantation of Hypoxic Preconditioned Neural Stem Cells Benefits Functional Recovery via Enhancing Neurotrophic Secretion after Spinal Cord Injury in Rats

Investigators showed that transplantation of hypoxic prconditioned neural stem cells (NSCs) could enhance neuronal survival, especially 5-TH⁺ and ChAT⁺ neurons, in the injured spinal cord to reinforce functional benefits. The hypoxia exposure upregulated HIF-1α, neurotrophic and growth factors including neurotrophin-3, glial cell-derived neurotrophic factor and brain-derived neurotrophic factor in vitro and in vivo. [J Cell Biochem] Abstract

Arctic Aβ40 Blocks the Nicotine-Induced Neuroprotective Effect of CHRNA7 by Inhibiting the ERK1/2 Pathway in Human Neuroblastoma Cells

Researchers investigated whether Arctic amyloid β protein (Aβ)40 affects neuronal survival and/or death via CHRNA7. Using human neuroblastoma SH-SY5Y cells, they found that the neuroprotective function of CHRNA7 is blocked by CHRNA7 knockdown using RNA interference. [Neurochem Int] Abstract | Graphical Abstract

Mdivi-1 Protects Adult Rat Hippocampal Neural Stem Cells against Palmitate-Induced Oxidative Stress and Apoptosis

Scientists examined the role of mdivi-1, a selective inhibitor of mitochondrial fission protein dynamin-regulated protein 1, on the survival of cultured hippocampal neural stem cells (NSCs) exposed to high palmitate. Treatment of hippocampal NSCs with mdivi-1 attenuated palmitate-induced increase in cell death and apoptosis. [Int J Mol Sci] Full Article

The Use of Brain Organoids to Investigate Neural Development and Disease

Recent advances in stem cell technologies that enable the generation of human brain organoids from pluripotent stem cells promise to profoundly change our understanding of the development of the human brain and enable a detailed study of the pathogenesis of inherited and acquired brain diseases. [Nat Rev Neurosci] Abstract

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Project ALS and Amylyx Enter Collaboration to Test AMX0035

Project ALS and Amylyx Pharmaceuticals announced a collaboration to undertake pre-clinical studies with Amylyx’s oral compound AMX0035 to advance the understanding of the compound’s neurobiological effects. The studies to be conducted at the Project ALS Pre-Clinical Core at Columbia University’s Motor Neuron Center will complement the company’s recently initiated Phase II clinical program of AMX0035 for the treatment of ALS. [Amylyx Pharmaceutical Corp.] Press Release

UBC Researchers Tackle Health Issues with $23.4 Million in CIHR Grants

Nine University of British Columbia (UBC) researchers have been awarded $23.4 million in funding through foundation grants from the Canadian Institutes of Health Research (CIHR). Their individual amounts range from approximately $500,000 to over $5 million. [University of British Columbia] Press Release

AgeneBio to Receive up to $10 Million in NIH Funding to Advance Program for Mild Cognitive Impairment Due to Alzheimer’s Disease

AgeneBio announced it has been awarded a grant for up to $10 million from the National Institute on Aging of the National Institutes of Health (NIH) to support its novel GABA_A discovery program to treat mild cognitive impairment due to Alzheimer’s disease and delay the onset of Alzheimer’s dementia. [AgeneBio, Inc.] Press Release

$9.5 Million in Grants to UVic Researchers Will Have Vital Impact

Cutting-edge research at the University of Victoria (UVic) got a big boost as Federal Science Minister Kirsty Duncan arrived on campus to announce $9.5 million in Natural Sciences and Engineering Research Council grants to 81 faculty members and students. [University of Victoria] Press Release

Oligomerix, Inc. Awarded National Institute on Aging SBIR Grant for Development of Alzheimer’s Disease Specific Biomarker

Oligomerix, Inc. announced the receipt of a Small Business Innovation Research (SBIR) Phase I grant for $302,112 from the National Institutes of Health, National Institute on Aging. [Oligomerix, Inc. (Business Wire, Inc.)] Press Release

Sage Therapeutics Reports Top-Line Results from Phase III STATUS Trial of Brexanolone in Super-Refractory Status Epilepticus

Sage Therapeutics reported top-line results from its Phase III STATUS Trial of brexanolone in the treatment super-refractory status epilepticus. The study did not meet the primary endpoint, comparing success in weaning of third-line agents and resolution of potentially life-threatening status epilepticus with brexanolone vs. placebo when added to standard-of-care. [Sage Therapeutics] Press Release | Editorial

DelMar Pharmaceuticals Initiates Phase II Clinical Trial in Newly Diagnosed MGMT-Unmethylated Glioblastoma Multiforme

DelMar Pharmaceuticals announced the initiation of a Phase II clinical trial for its lead agent VAL-083 in newly diagnosed MGMT-unmethylated glioblastoma multiforme (GBM). The biomarker-driven clinical trial will explore safety and efficacy of chemoradiation with VAL-083 as an alternative to standard-of-care temozolomide in patients with MGMT-unmethylated GBM. [DelMar Pharmaceuticals, Inc.] Press Release

Voyager Therapeutics Announces Positive Results from Ongoing Phase Ib Trial of Vy-AADC01 for Advanced Parkinson’s Disease

Voyager Therapeutics, Inc. announced positive results from its ongoing Phase Ib trial of VY-AADC01 in advanced Parkinson’s disease. The results demonstrated durable, dose-dependent and time-dependent improvements across multiple measures of patients’ motor function after a one-time administration of the gene therapy. [Voyager Therapeutics, Inc.] Press Release

Neuraltus Pharmaceuticals and the University of Hawaii at Manoa Announce Initiation of Phase Ib Study of NP001 in Patients with Mild-to-Moderate Alzheimer’s Disease

Neuraltus Pharmaceuticals, Inc. and the John A. Burns School of Medicine, University of Hawaii at Manoa announced the initiation of a Phase Ib placebo-controlled biomarker study of the company’s investigational therapy, NP001, in individuals with Alzheimer’s disease. [Neuraltus Pharmaceuticals, Inc. (PR Newswire Association LLC.)] Press Release

Nativis Announces Expanded Clinical Program in Glioblastoma Multiforme

Nativis, Inc. announced expansion of its clinical program in glioblastoma multiforme (GBM). Chris Rivera, Nativis President and Chief Executive Officer, announced that based on encouraging safety and survival data, the current feasibility study in recurrent GBM, NAT-101, will be expanded to enroll up to 32 more patients in the combination therapy arm – i.e., Nativis Voyager^® plus a standard chemotherapy drug. [Nativis, Inc.] Press Release

Congress Rejects Trump Proposals to Cut Health Research Funds

Congress has not only rejected the president’s National Institutes of Health proposal; lawmakers from both parties have joined forces to increase spending on biomedical research — and have bragged about it. [The New York Times] Editorial

Pall Hangs over U.S.-Iran Science Ties

Rising tensions between the U.S. and Iranian governments have frozen most scientific contacts between the two nations, experts reported at a forum. [ScienceInsider] Editorial

Senate Panel Seeks Middle Ground on Human Fetal Tissue Research and Abortion

A Senate spending panel countered a move by its House of Representatives counterpart to quash federal funding for research that uses human fetal tissue from elective abortions. The move sets up a conflict that will need to be resolved when lawmakers meet later this year to hash out differences between the House and Senate bills, which will provide funding for the National Institutes of Health in the 2018 fiscal year. [ScienceInsider] Editorial

NEW Cold Spring Harbor (CSH): Development and 3-D Modeling of the Human Brain
December 6-9, 2017
Cold Spring Harbor, New York, United States

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NEW 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 Researchers – Glial Cells (University of California, Davis)

Faculty Scientists – Neuroscience (Cedars-Sinai Medical Center)

Postdoctoral Fellow – Neural Regeneration (Johns Hopkins University)

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

Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma)

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