Neural Cell News Volume 13.30 | Aug 7 2019

TOP STORY

IMP Dehydrogenase-2 Drives Aberrant Nucleolar Activity and Promotes Tumorigenesis in Glioblastoma

Investigators showed that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, was overexpressed in the highly lethal brain cancer glioblastoma. Impairment of IMPDH2 activity triggered nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. [Nat Cell Biol] Abstract | Press Release

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Targeting Pyrimidine Synthesis Accentuates Molecular Therapy Response in Glioblastoma Stem Cells

Targeting the pyrimidine synthetic rate-limiting step enzyme carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, dihydroorotase or the critical downstream enzyme dihydroorotate dehydrogenase inhibited glioblastoma stem cell survival, self-renewal, and in vivo tumor initiation through the depletion of the pyrimidine nucleotide supply in rodent models. [Sci Transl Med] Abstract

Inhibition of Axon Regeneration by Liquid-Like TIAR-2 Granules

Researchers demonstrated an in vivo function for phase-separated TIAR-2 and identified features critical for its function in axon regeneration. [Neuron] Abstract | Graphical Abstract

ADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS

Investigators explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. [Neuron] Abstract | Graphical Abstract

Haploinsufficiency in the ANKS1B Gene Encoding AIDA-1 Leads to a Neurodevelopmental Syndrome

Neurons generated from patient-derived induced pluripotent stem cells demonstrated loss of the ANKS1B-encoded protein AIDA-1, a brain-specific protein highly enriched at neuronal synapses. [Nat Commun] Full Article

Modeling Single-Molecule Conformations of the HoxD Region in Mouse Embryonic Stem and Cortical Neuronal Cells

Scientists revealed the mode of action of compartmentalization on the regulation of the HoxD genes that had gene- and cell-type-specific multi-way interactions with their regulatory elements and high cell-to-cell variability. [Cell Rep] Abstract | Graphical Abstract

Id4 Downstream of Notch2 Maintains Neural Stem Cell Quiescence in the Adult Hippocampus

Researchers found that Id4 was a downstream target of Notch2 signaling and maintained dentate gyrus (DG) neural stem cell (NSC) quiescence by blocking cell-cycle entry. Id4 expression was sufficient to promote DG NSC quiescence and Id4 knockdown rescued Notch2-induced inhibition of NSC proliferation. [Cell Rep] Full Article | Graphical Abstract

Tumor-Treating Fields Induce Autophagy by Blocking the Akt2/miR29b Axis in Glioblastoma Cells

Investigators showed that the activation of autophagy contributes to the tumor-treating field-induced anti-glioblastoma multiforme (GBM) activity in vitro or in vivo and GBM patient stem cells or primary in vivo culture systems. [Oncogene] Abstract

miR-425 Deficiency Promotes Necroptosis and Dopaminergic Neurodegeneration in Parkinson’s Disease

The authors found that miR-425 deficiency triggered necroptosis of dopaminergic neurons, and targeting miR-425 in MPTP-treated mice restored dysfunctional dopaminergic neurodegeneration and ameliorated behavioral deficits. [Cell Death Dis] Full Article

Long-Term Safety, Immunologic Response, and Imaging Outcomes following Neural Stem Cell Transplantation for Pelizaeus-Merzbacher Disease

Four boys with Pelizaeus-Merzbacher disease, an X-linked leukodystrophy, underwent transplantation with human allogeneic central nervous system stem cells. Subsequently, all subjects were followed for an additional four years in this separate follow-up study to evaluate safety, neurologic function, magnetic resonance imaging data, and immunologic response. [Stem Cell Reports] Full Article

Neurons-Derived Extracellular Vesicles Promote Neural Differentiation of ADSCs: A Model to Prevent Peripheral Nerve Degeneration

The authors demonstrated that adipocyte derived stem cells (ADSCs) in indirect contact with neurons differentiated into neuron-like cells. Neuron-derived extracellular vesicles appeared to play an important role in this process carrying SNAP25, miR-132 and miR-9. [Sci Rep] Full Article

Reversibility of Age-Related Oxidized Free NADH Redox States in Alzheimer’s Disease Neurons by Imposed External Cys/CySS Redox Shifts

Scientists examined the flexibility of mitochondrial-specific free NADH in live neurons from non-transgenic or triple transgenic Alzheimer’s disease-like mice of different ages under an imposed extracellular cysteine/cystine (Cys/CySS) oxidative or reductive condition. [Sci Rep] Full Article

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Modeling Alzheimer’s Disease with iPSC-Derived Brain Cells

Many cellular functions perturbed in Alzheimer’s disease can be recapitulated using induced pluripotent stem cell (iPSC)-derived cells in vitro, and co-culture platforms are beginning to yield insights into the complex interactions that occur between brain cell types during neurodegeneration. [Mol Psychiatry] Full Article

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AZTherapies Completes Enrollment in COGNITE Pivotal Phase III Trial of ALZT-OP1 for the Treatment of Early Alzheimer’s Disease

AZTherapies, Inc. announced that it has completed target enrollment in its COGNITE Phase III clinical trial, evaluating the safety and efficacy of ALZT-OP1 for the treatment of early Alzheimer’s disease. [AZTherapies, Inc.] Press Release

AC Immune Initiates PhIb/IIa Study of Anti-Phospho-Tau Vaccine in Alzheimer’s Disease

AC Immune SA announced the initiation of a Phase Ib/IIa clinical trial to evaluate ACI-35.030, an anti-phospho-Tau vaccine. ACI-35.030 targets pathological Tau and is intended as a disease-modifying treatment for Alzheimer’s disease and other Tauopathies. [AC Immune SA] Press Release

Rewind Therapeutics Awarded €2.9 Million VLAIO Grant to Discover and Develop Novel Drug Candidates for Myelin-Related Neurological Diseases

Rewind Therapeutics announced it will lead a new industry-academic R&D collaboration to discover and develop first-in-class inhibitors of a key G protein-coupled receptor target that has an influential role in myelin-related neurological diseases. [Rewind Therapeutics (PR Newswire Association LLC.)] Press Release

Novartis CEO: ‘We Tried to Do the Right Things’ in FDA Data Scandal

Novartis CEO Vas Narasimhan defended his company’s decision to wait three months to tell authorities about falsified data submitted to the FDA, saying the company “tried to do the right things” in the process. He also said Novartis was now “in the process of exiting” a small number of scientists at AveXis, Novartis’s gene therapy business, who were involved in these data inaccuracies. [STAT News] Editorial

First Human-Monkey Chimeras Developed in China

Juan Carlos Izpisúa Belmonte of the Salk Institute in San Diego is spearheading the project with scientists from his own lab and those from the Murcia Catholic University in Murcia, Spain. The team wants to develop chimeras—organisms composed of cells from two or more species—capable of growing human organs. [The Scientist] Editorial

NEW Development and 3D Modeling of the Human Brain
December 9-12, 2019
Cold Spring Harbor, New York, United States

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NEW Postdoctoral Research Fellow – Psychiatric Disorders (McLean Hospital)

Scientific Communications Coordinator (STEMCELL Technologies Inc.)

Postdoctoral Associate – Cerebral Organoids (Weill Cornell Medicine)

Tenure-Track Assistant Professor – Cognitive Neuroscience (Lawrence University of Wisconsin)

Postdoctoral Fellowship – Neurogenesis & Neural Cell Aging (Lund University)

Postdoctoral Fellowship – Bioinformatics & Neurogenesis (Lund University)

Postdoctoral Fellowship – Reprogramming Glioblastoma (Lund University)

Postdoctoral Scientist – Glioma Organoids (Rutgers Cancer Institute of New Jersey)

Research Lab Specialist – Tumor Microenvironment & Cell Behavior (University of Southern California)

Tenure Track Faculty Positions – Neuropharmacology or Neurodegeneration (The University of Tennessee Health Science Center)

Postdoctoral Researcher – Retinal Stem Cell Biology (NIH National Eye Institute)

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