Neural Cell News Volume 13.08 | Mar 6 2019

TOP STORY

Quiescence Modulates Stem Cell Maintenance and Regenerative Capacity in the Aging Brain

Scientists report a dramatic drop in neural stem cell (NSC) number in the aging murine brain. They found that this smaller stem cell reservoir was protected from full depletion by an increase in quiescence that makes old NSCs more resistant to regenerate the injured brain. Once activated, however, young and old NSCs showed similar proliferation and differentiation capacity. [Cell] Abstract | Press Release | Graphical Abstract

(Ranked by impact factor of the journal)

Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair

Ionizing radiation and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. Researchers identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (Y240) by FGFR2. Blocking Y240 phosphorylation conferred radiation sensitivity to tumors and extended survival in GBM preclinical models. [Cancer Cell] Abstract | Press Release | Graphical Abstract

ACVR1 R206H Cooperates with H3.1K27M in Promoting Diffuse Intrinsic Pontine Glioma Pathogenesis

Treatment of ACVR1 R206H mutant diffuse intrinsic pontine gliomas (DIPGs) with exogenous Noggin or the ACVR1 inhibitor LDN212854 significantly prolonged survival, with human ACVR1 mutant DIPG cell lines also being sensitive to LDN212854 treatment. [Nat Commun] Full Article

Down-Regulated TMED10 in Alzheimer’s Disease Induces Autophagy via ATG4B Activation

Protein-protein interaction assays showed that transmembrane p24 trafficking protein 10 (TMED10) directly bound to autophagy related gene 4B cysteine peptidase (ATG4B), and the interaction was diminished under autophagy activation conditions such as rapamycin treatment and serum deprivation. [Autophagy] Abstract

NrCAM Is a Marker for Substrate-Selective Activation of ADAM10 in Alzheimer’s Disease

ADAM10 controlled NrCAM surface levels and regulated neurite outgrowth in vitro in an NrCAM-dependent manner. However, ADAM10 cleavage of NrCAM, in contrast to amyloid precursor protein, was not stimulated by the ADAM10 activator acitretin, suggesting that substrate-selective ADAM10 activation may be feasible. [EMBO Mol Med] Full Article

Lipid Transporter TMEM24/C2CD2L Is a Ca²⁺-Regulated Component of ER-Plasma Membrane Contacts in Mammalian Neurons

TMEM24 was enriched in neurons versus glial cells and its levels increased in parallel with neuronal differentiation. It populated endoplasmic reticulum (ER)-plasma membrane contacts in resting neurons, but elevations of cytosolic Ca²⁺ mediated by experimental manipulations or spontaneous activity induced its transient redistribution throughout the entire ER. [Proc Natl Acad Sci USA] Abstract

SorCS2 Controls Functional Expression of Amino Acid Transporter EAAT3 and Protects Neurons from Oxidative Stress and Epilepsy-Induced Pathology

The authors showed that SorCS2 acted as sorting receptor that sustained cell surface expression of the neuronal amino acid transporter EAAT3 to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Lack of SorCS2 caused depletion of EAAT3 from the plasma membrane and impaired neuronal cysteine uptake. [Cell Rep] Full Article | Graphical Abstract

FMR1 Reactivating Treatments in Fragile X iPSC-Derived Neural Progenitors In Vitro and In Vivo

In order to investigate the regulatory layers involved in FMR1 inactivation, investigators tested a collection of chromatin modulators for the ability to reactivate the FMR1 locus. Although inhibitors of DNA methyltransferase (DNMT) induced the highest levels of FMR1 expression, a combination of a DNMT inhibitor and another compound potentiated the effect of reactivating treatment. [Cell Rep] Full Article | Graphical Abstract

SQSTM1/p62-Directed Metabolic Reprogramming Is Essential for Normal Neurodifferentiation

Researchers suggest that p62 was essential for neuronal differentiation by controlling the metabolic shift from aerobic glycolysis to oxidative phosphorylation required for neuronal maturation. This shift was blocked by failure to sufficiently downregulate lactate dehydrogenase expression due to the loss of p62, possibly through impaired Hif-1α downregulation and increased sensitivity to oxidative stress. [Stem Cell Reports] Full Article | Graphical Abstract

Foxg1 Antagonizes Neocortical Stem Cell Progression to Astrogenesis

Investigators showed that high Foxg1 stem cell (SC) expression antagonized astrocyte generation, while stimulating SC self-renewal and committing SCs to neuronogenesis. They found that mechanisms underlying this activity were mainly cell autonomous and highly pleiotropic. [Cereb Cortex] Abstract | Press Release

Cellular Energy Stress Induces AMPK-Mediated Regulation of Glioblastoma Cell Proliferation by PIKE-A Phosphorylation

The authors showed that cellular energy stress induced phosphoinositide 3-kinase enhancer-activating Akt (PIKE-A) phosphorylation mediated by AMP-activated protein kinase (AMPK) activation, thereby preventing its carcinogenic action. [Cell Death Dis] Full Article

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Novel Electrode Technologies for Neural Recordings

Scientists describe how emergent neurotechnologies can approach the ultimate goal of illuminating chronic brain activity with minimal disruption of the neural environment, thereby providing unprecedented opportunities for neuroscience research in the future. [Nat Rev Neurosci] Abstract

Preserving the Balance: Diverse Forms of Long-Term GABAergic Synaptic Plasticity

A growing body of literature demonstrates the capacity for inhibitory GABAergic synapses to exhibit long-term plasticity in response to changes in neuronal activity. Here, the authors review this expanding field of research, focusing on the diversity of mechanisms that link glutamatergic signaling, postsynaptic action potentials and inhibitory synaptic strength. [Nat Rev Neurosci] Abstract

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

Principia Biopharma Presents Phase I Clinical Data from CNS Penetrating BTK Inhibitor Candidate PRN2246/SAR442168

Principia Biopharma Inc. announced the presentation of Phase I clinical data for PRN2246, now known as SAR442168. [Press release from Principia Biopharma Inc. discussing research presented at the American Consortium for Therapy and Research in Multiple Sclerosis (ACTRIMS) Annual Meeting, Dallas] Press Release

Odonate Therapeutics Announces Presentation

Odonate Therapeutics, Inc. announced the acceptance for presentation of an abstract describing results of preclinical studies of tesetaxel, Odonate’s investigational, orally administered taxane. [Press release from Odonate Therapeutics, Inc. discussing research to be presented at the American Association for Cancer Research (AACR) Annual Meeting, Atlanta] Press Release

Marinus Pharmaceuticals Initiates Phase III Study in Children with PCDH19-Related Epilepsy

Marinus Pharmaceuticals, Inc. announced that it is initiating a single global pivotal Phase III clinical study evaluating oral ganaxolone in children with PCDH19-related epilepsy, a rare genetic epilepsy. [Marinus Pharmaceuticals, Inc.] Press Release

Oncotelic Reports Clinical Validation of Drug Induce Xenogenization (DIX) for Treatment of Glioblastoma and Pancreatic Cancer (PC)

Oncotelic announced clinical data supporting the use of chemotherapy-induced Xenogenization for the in situ immunization against glioblastoma and PC. [Oncotelic (GlobeNewswire, Inc.)] Press Release

Mitochon Pharmaceuticals Awarded Orphan Drug Designation

Mitochon Pharmaceuticals announced that it was awarded Orphan Drug Designation by FDA for its mitochondrial targeted compound, MP-101 for treating Huntington’s Disease. [Mitochon Pharmaceuticals] Press Release

UCI Researcher Awarded Nearly $4 Million for Studies Related to Neurological Disorders including Epilepsy

University of California, Irvine (UCI) School of Medicine researcher Geoff Abbott, PhD, has been awarded a $2 million Outstanding Investigator Award/Maximizing Investigators’ Research Award R35 grant from the National Institute of General Medical Sciences, and a $1.7 million R01 grant from the National Institute of Neurological Disorders and Stroke. [University of California, Irvine] Press Release

Wake Forest Baptist Receives NIH Grant to Study Deep Brain Stimulation for Alzheimer’s

Scientists at Wake Forest Baptist Health have been awarded $3.9 million from the National Institutes of Health (NH) to determine if a procedure used to treat Parkinson’s patients can improve age-related cognitive abilities and counteract the effects of Alzheimer’s and other types of dementia. [Wake Forest Baptist Medical Center] Press Release

MSU Lands $5M NIH Grant to Connect Dots between Pesticides and Parkinson’s

Honglei Chen, a professor of epidemiology whose research focuses on neurodegenerative diseases, will use a five-year, $5 million grant from the National Institutes for Health (NIH) to investigate the role pesticides might play in olfactory impairment and their relevance to diseases such as Alzheimer’s and Parkinson’s. [Michigan State University] Press Release

Vect-Horus and RadioMedix Announce the Signing of a LOI to Co-Develop a Vect-Horus’ Radio-Theranostic Agent for Glioblastoma

Vect-Horus and RadioMedix announced the signing of a Letter of Intent (LOI) to establish an agreement for the co-development of a Vect-Horus theranostic agent for the diagnostic and radiotherapy of Glioblastoma Multiforme of the brain. [Vect-Horus (Business Wire, Inc.)] Press Release

Head of US Food and Drug Agency Resigns

Scott Gottlieb, the head of the US Food and Drug Administration (FDA), resigned on 5 March and will depart the agency in one month. [Nature News] Editorial | Opinion

China Creating National Medical Ethics Committee to Oversee High-Risk Clinical Trials

A powerful new national medical ethics committee, which will approve all clinical trials involving high-risk biomedical technologies, is at the center of a regulatory shakeup Chinese authorities are planning in the aftermath of the widely condemned “CRISPR babies” experiment, STAT has learned. [STAT News] Editorial

NEW EMBO-EMBL: The Identity & Evolution of Cell Types
May 15-18, 2019
Heidelberg, Germany

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NEW Research Associate – iPSC & Neurodegenerative Disease (TU Dresden)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Researcher Position – Circuit & Behavioral Neuroscience (Instituto Italiano di Tecnologia)

Postdoctoral Positions – Neurodegeneration (Van Andel Research Institute)

Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Position – Neurophysiology (University Medical Center Hamburg Eppendorf)

Post Doctoral Scholarship – Brain Tumor Biology (Lund University)

Postdoctoral Scholar – Brain Tumor Biology (Lund University)

Faculty Positions – Developmental Neurosciences (Kent State University)

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)

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