Neural Cell News Volume 13.03 | Jan 30 2019

TOP STORY

Onset of Differentiation Is Post-Transcriptionally Controlled in Adult Neural Stem Cells

The generation of neurogenic progeny involved translational repression of a subset of mRNAs, including mRNAs that encode the stem cell identity factors SOX2 and PAX6, and components of the translation machinery, which are enriched in a pyrimidine-rich motif. The decrease of mTORC1 activity as stem cells exited the cell cycle selectively blocked translation of these transcripts. [Nature] Abstract

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Cholesterol Metabolism Is a Druggable Axis that Independently Regulates Tau and Amyloid-β in iPSC-Derived Alzheimer’s Disease Neurons

Efficacy and toxicity screening in induced pluripotent stem cell (iPSC)-derived astrocytes and neurons showed that allosteric activation of CYP46A1 lowered cholesteryl esters specifically in neurons and was well tolerated by astrocytes. [Cell Stem Cell] Full Article | Press Release | Graphical Abstract

Differentiation and Maturation of Oligodendrocytes in Human Three-Dimensional Neural Cultures

Investigators developed a new differentiation method of human induced pluripotent stem cells to generate 3D brain organoids that contain oligodendrocytes as well as neurons and astrocytes, called human oligodendrocyte spheroids. [Nat Neurosci] Abstract | Press Release

FGL2 Promotes Tumor Progression in the CNS by Suppressing CD103⁺ Dendritic Cell Differentiation

Researchers showed that fibrinogen-like protein 2 (FGL2) was highly expressed in glioma stem cells and primary glioblastoma (GBM) cells. FGL2 knockout in tumor cells did not affect tumor cell proliferation in vitro or tumor progression in immunodeficient mice but completely impaired GBM progression in immune-competent mice. [Nat Commun] Full Article | Press Release

The Functional Synergism of MicroRNA Clustering Provides Therapeutically Relevant Epigenetic Interference in Glioblastoma

Synchronizing the expression of three microRNAs in a gene therapy approach displayed significant anticancer synergism, abrogated this epigenetic-mediated, multi-protein tumor survival mechanism and resulted in a five-fold increase in survival when combined with chemotherapy in murine glioblastoma models. [Nat Commun] Full Article | Press Releae

Abnormal TDP-43 Function Impairs Activity-Dependent BDNF Secretion, Synaptic Plasticity, and Cognitive Behavior through Altered Sortilin Splicing

Human neurons derived from patient iPSCs carrying mutated TDP-43 showed altered sortilin splicing and reduced levels of activity-dependent brain-derived neurotrophic factor (BDNF) secretion, which could be restored by correcting the mutation. [EMBO J] Abstract | Graphical Abstract

Atoh1 Controls Primary Cilia Formation to Allow for SHH-Triggered Granule Neuron Progenitor Proliferation

Loss of primary cilia abolished the ability of Atoh1 to keep granule neuron progenitors in a proliferative state. Mechanistically, Atoh1 promoted ciliogenesis by transcriptionally regulating Cep131, which facilitates centriolar satellite clustering to the basal body. [Dev Cell] Abstract | Graphical Abstract

Enhancer Histone Acetylation Modulates Transcriptional Bursting Dynamics of Neuronal Activity-Inducible Genes

Investigators expressed dCas9-p300 or dCas9-HDAC8 fusion proteins to mimic or block activity-induced histone acetylation locally at enhancers. Adding histone acetylation increased Fos transcription by prolonging burst duration and resulted in higher Fos protein levels and an elevation of resting membrane potential. [Cell Rep] Full Article | Graphical Abstract

REST and Neural Gene Network Dysregulation in iPSC Models of Alzheimer’s Disease

The induced pluripotent stem cell (iPSC)-derived neural cells from sporadic Alzheimer’s disease patients exhibited accelerated neural differentiation and reduced progenitor cell renewal. Moreover, a similar phenotype appeared in Alzheimer’s disease cells and cerebral organoids derived from apolipoprotein E4 iPSCs. [Cell Rep] Full Article | Press Release | Graphical Abstract

Isolation and Characterization of Patient-Derived CNS Metastasis-Associated Stromal Cell Lines

Four different patient-derived cell lines (PDCs) of stromal and one PDC of tumorigenic origin were generated from breast or lung CNS metastases. PDCs were analyzed by DNA/RNA sequencing, DNA methylation profiling, and immunophenotypic assays. [Oncogene] Full Article

Neuropilin-1-Mediated Pruning of Corticospinal Tract Fibers Is Required for Motor Recovery after Spinal Cord Injury

Scientists observed that neuropilin-1 (Nrp1) mRNA was upregulated in layer five pyramidal neurons in the motor cortex 14 days after spinal cord injury (SCI), when the pruning occurred. Nrp1 knockdown using adeno-associated virus vector encoding Nrp1 shRNA in the hindlimb motor area impaired the pruning of collaterals after SCI. [Cell Death Dis] Full Article

Selective Inhibition of Mitochondrial Sodium-Calcium Exchanger Protects Striatal Neurons from α-Synuclein plus Rotenone Induced Toxicity

Electrophysiological recordings of field postsynaptic potentials and Ca²⁺ measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-synuclein and the neurotoxic pesticide rotenone induced Ca²⁺ dysregulation and alteration of both synaptic transmission and cell function. The presence of the mitochondrial NCX inhibitor CGP-37157 prevented these alterations. [Cell Death Dis] Full Article

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How the Epigenome Integrates Information and Reshapes the Synapse

Investigators explore how epigenetic mechanisms give rise to stable alterations in neuronal function by modifying synaptic structure and function, and highlight studies that demonstrate how manipulating epigenetic mechanisms may push the boundaries of memory. [Nat Rev Neurosci] Abstract

Exosomes – Beyond Stem Cells for Restorative Therapy in Stroke and Neurological Injury

The authors consider the opportunities for exosome-based approaches to therapeutic amplification of brain repair and improvement of recovery after stroke, traumatic brain injury and other diseases in which neurorestoration could be a viable treatment strategy. [Nat Rev Neurol] Abstract

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

Neurocrine Biosciences and Voyager Therapeutics Form Strategic Development and Commercialization Collaboration for Parkinson’s Disease and Friedreich’s Ataxia

Neurocrine Biosciences, Inc. and Voyager Therapeutics, Inc. announced the formation of a strategic collaboration focused on the development and commercialization of Voyager’s gene therapy programs, VY-AADC for Parkinson’s disease and VY-FXN01 for Friedreich’s ataxia, as well as rights to two programs to be determined. [Neurocrine Biosciences, Inc.] Press Release

Roche to Discontinue Phase III CREAD 1 and 2 Clinical Studies of Crenezumab in Early Alzheimer’s Disease (AD) – Other Company Programs in AD Continue

Roche announced the decision to discontinue CREAD I and CREAD 2 Phase III studies of the investigational anti-beta-amyloid molecule crenezumab in people with early sporadic AD. [F. Hoffmann-La Roche Ltd] Press Release

John Theurer Cancer Center Leading Enrollment for Global Phase II WIZARD Study Evaluating DSP-7888 in Patients with Recurrent Glioblastoma

John Theurer Cancer Center at Hackensack Meridian Health Hackensack University Medical Center announced that it is leading enrollment worldwide for WIZARD 201G, a global Phase II study in glioblastoma. The trial, sponsored by Boston Biomedical, is evaluating DSP-7888, an investigational cancer vaccine, in combination with bevacizumab for recurrent disease. [Hackensack Meridian Health] Press Release

First US Patient in Novel Stem Cell Trial for Stroke Disability Enrolled at UTHealth

The trial, called PISCES III, is a Phase IIb, randomized, placebo-controlled, multicenter study enrolling a total of 110 eligible ischemic stroke patients, age 35 to 75, who are experiencing persistent disability 6 to 12 months post-stroke. [The University of Texas Health Science Center at Houston (UTHealth)] Press Release

Ironwood Pharmaceuticals Initiates Phase I Trial of IW-6463, the First CNS-Penetrant sGC Stimulator to Enter Clinical Trials

Ironwood Pharmaceuticals, Inc. announced the initiation of a Phase I study evaluating IW-6463 in healthy volunteers. IW-6463 is an orally administered central nervous system (CNS)-penetrant soluble guanylate cyclase (sGC) stimulator that is being developed for the treatment of serious and orphan CNS disorders. [Ironwood Pharmaceuticals, Inc.] Press Release

Alzheimer’s Association Funds Two-Year Extension of the SPRINT MIND Study

The Alzheimer’s Association has awarded more than $800,000 to support the SPRINT MIND 2.0 Study, which will further investigate the impact of intensive blood pressure treatment on reducing risk of dementia. The newly funded study will continue and extend follow up of the SPRINT MIND trial participants. [Alzheimer’s Association] Press Release

What are ‘mini-brains’, and how are they being used to study neurological development and disease? Watch Now

US Government Shutdown’s Effects on Science Ripple Overseas

From canceled conferences to delayed publications, fallout of the shutdown spread beyond US borders, prompting concerns about long-term damage to international collaboration. [The Scientist] Editorial

How Brexit Threatens Irish Science’s Cross-Border Collaboration

Scientists in Northern Ireland and the Republic of Ireland are worried that Brexit will upset the island’s research ecosystem, which has benefited from peace and economic growth over the past 20 years. [Nature News] Editorial

NEW The 14^th International Conference on Alzheimer’s & Parkinson’s Diseases (AD/PD^TM 2019)
March 26-31, 2019
Lisbon, Portugal

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NEW Postdoctoral Scholar – Brain Tumor Biology (Lund University)

NEW Faculty Positions – Developmental Neurosciences (Kent State University)

NEW Postdoctoral Scientist – Regenerative Plasticity of Neural Circuits (Cedars-Sinai Medical Center)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Assistant Member – Developmental Neurobiology (St. Jude Children’s Research Hospital)

Research Assistant – Cellular Neuroscience (Cardiff University)

Research Fellow – Neuroscience (University College London)

Associate Professor/Assistant Professor – Neuroscience (Hong Kong Baptist University)

Postdoctoral Fellowship – Alzheimer’s & Cerebrovascular Disease (Schepens Eye Research Institute/Massachusetts Eye and Eaar)

PhD – Neuroscience (Institute for Neuroscience)

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