Neural Cell News Volume 13.15 | Apr 24 2019

TOP STORY

Neuronal Deletion of Gtf2i, Associated with Williams Syndrome, Causes Behavioral and Myelin Alterations Rescuable by a Remyelinating Drug

Researchers showed that selective deletion of general transcription factor IIi (Gtf2i) in the excitatory neurons of the forebrain caused neuroanatomical defects, fine motor deficits, increased sociability and anxiety. [Nat Neurosci] Abstract | Press Release

(Ranked by impact factor of the journal)

Bassoon Proteinopathy Drives Neurodegeneration in Multiple Sclerosis

Neuronal overexpression of bassoon (Bsn) in flies resulted in reduction of lifespan, while genetic disruption of Bsn protected mice from inflammation-induced neuroaxonal injury. Notably, pharmacological proteasome activation boosted the clearance of accumulated Bsn and enhanced neuronal survival. [Nat Neurosci] Abstract | Press Release

Galectin-3, a Novel Endogenous TREM2 Ligand, Detrimentally Regulates Inflammatory Response in Alzheimer’s Disease

In vitro data revealed that galectin-3 (gal3) was required to fully activate microglia in response to fibrillar amyloid beta (Aβ). Interestingly, a single intrahippocampal injection of gal3 along with Aβ monomers in wildtype mice was sufficient to induce the formation of long-lasting insoluble Aβ aggregates, which were absent when gal3 was lacking. [Acta Neuropathol] Full Article

iPSC-Derived Homogeneous Populations of Developing Schizophrenia Cortical Interneurons Have Compromised Mitochondrial Function

Scientists generated homogeneous populations of developing cortical interneurons (cINs) from 15 healthy control induced pluripotent stem cell (iPSC) lines and 15 schizophrenia (SCZ) iPSC lines. SCZ cINs, but not SCZ glutamatergic neurons, showed dysregulated oxidative phosphorylation related gene expression, accompanied by compromised mitochondrial function. [Mol Psychiatry] Abstract

Extraciliary Roles of the Ciliopathy Protein JBTS17 in Mitosis and Neurogenesis

The authors examined the potential roles of JBTS17 in neurogenesis to understand the pathological mechanism of JBTS17-related cortical abnormalities. They performed knockdown experiments to determined roles of JBTS17 in human cells, and demonstrated mitotic functions of JBTS17 using immunostaining and live imaging. [Ann Neurol] Abstract

α-Sheet Secondary Structure in Amyloid β-Peptide Drives Aggregation and Toxicity in Alzheimer’s Disease

Researchers showed, by a variety of different techniques, that amyloid β-peptide (Aβ) oligomers adopt a nonstandard secondary structure, termed “α-sheet.” These oligomers formed in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils. [Proc Natl Acad Sci USA] Abstract | Editorial

Intrinsic Mutant HTT-Mediated Defects in Oligodendroglia Cause Myelination Deficits and Behavioral Abnormalities in Huntington Disease

Investigators showed that selective inactivation of mutant huntingtin (mHTT) in the NG2⁺ oligodendrocyte progenitor cell population prevented myelin abnormalities and certain behavioral deficits in Huntington disease mice. Strikingly, the improvements in behavioral outcomes were seen despite the continued expression of mHTT in nonoligodendroglial cells including neurons, astrocytes, and microglia. [Proc Natl Acad Sci USA] Abstract

Most Clinical Anti-EGFR Antibodies Do Not Neutralize Both wtEGFR and EGFRvIII Activation in Glioma

Scientists re-assessed the activity of clinical epidermal growth factor receptor (EGFR) antibodies in patient-derived gliomaspheres that endogenously express EGFRvIII. The anti-tumor efficacy of the antibodies was assessed using in vitro proliferation assays and intracranial orthografts. [Neuro Oncol] Abstract

Regulation of the Apical Extension Morphogenesis Tunes the Mechanosensory Response of Microvilliated Neurons

The authors revealed that cerebrospinal fluid-contacting neurons are atypical neurons that do not lose their apical attachment and form a ring of actin at the apical junctional complexes that they retain during differentiation. [PLoS Biol] Full Article

The Integrator Complex Prevents Dedifferentiation of Intermediate Neural Progenitors Back into Neural Stem Cells

Loss of intS5, intS8, and intS1 generated ectopic type II neuroblasts. Intermediate neural progenitor (INP)-specific knockdown of intS8, intS1, and intS2 resulted in the formation of excess type II neuroblasts, indicating that integrator prevented INP dedifferentiation. [Cell Rep] Full Article | Press Release | Graphical Abstract

PAD2-Mediated Citrullination Contributes to Efficient Oligodendrocyte Differentiation and Myelination

Researchers showed that citrullination by peptidylarginine deiminase 2 (PAD2) contributed to normal oligodendrocyte differentiation, myelination, and motor function. They identified several targets for PAD2, including myelin and chromatin-related proteins, implicating PAD2 in epigenomic regulation. [Cell Rep] Full Article | Graphical Abstract

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Roles of Axon Guidance Molecules in Neuronal Wiring in the Developing Spinal Cord

An integrated view of spinal cord network development is lacking, and many current models have neglected the cellular and functional diversity of spinal cord circuits. Recent advances challenge the existing spinal cord axon guidance dogmas and have provided a more complex, but more faithful, picture of the ontogenesis of vertebrate spinal cord circuits. [Nat Rev Neurosci] Abstract

Disruption of RNA Metabolism in Neurological Diseases and Emerging Therapeutic Interventions

The authors describe distinct mechanisms by which the homeostasis of RNA binding proteins is compromised in neurological disorders through their reduced expression level, increased propensity to aggregate or sequestration by abnormal RNAs. [Neuron] Full Article

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

Eisai to Present Latest Data on Lemborexant and Perampanel

Eisai Co., Ltd. announced that the latest data on its dual orexin receptor antagonist lemborexant and its antiepileptic drug perampanel will be presented. [Press release from Eisai Co., Ltd. discussing research to be presented at the 2019 Annual American Academy of Neurology (AAN) Meeting, Philadelphia] Press Release

Project ALS and Columbia University Announce the Project ALS Therapeutics Core at Columbia

Columbia University and Project ALS announced the Project ALS Therapeutics Core at Columbia, a 3-year, $6.3M initiative toward the first meaningful therapies for ALS. The Core is the world’s first and only partnership between a world-class academic institution and a leading nonprofit organization dedicated to a full-spectrum approach to ALS drug development, preclinical evaluation, and human clinical trials. [Project ALS] Press Release

Mateon Enters into Merger Agreement with Oncotelic

Mateon Therapeutics, Inc. and Oncotelic Inc. announced that they have entered into a definitive agreement with respect to a merger, creating a publicly traded immuno-oncology company with a robust pipeline of first in class TGF-β immunotherapies for late stage cancers such as gliomas, pancreatic cancer and melanoma. [Mateon Therapeutics, Inc.] Press Release

Alector Announces First Frontotemporal Dementia Patient Dosed in Phase Ib Study of AL001

Alector, Inc. announced dosing of the first frontotemporal dementia patient in the Phase 1b portion of the INFRONT clinical study of AL001 after successful completion of the healthy volunteer single ascending dose escalation portion of the study. [Alector, Inc.] Press Release

Biogen Cans Plan to Test Aducanumab in Alzheimer’s Prevention

Biogen has decided against starting a Phase III trial of aducanumab in the prevention of Alzheimer’s disease. The study was the one option for further development of aducanumab that Biogen left open when it revealed the failure of its main pivotal program last month. [Biogen (FierceBiotech)] Press Release

TAU BIO-LOGIC Announces Humanization of Picomolar Affinity Monoclonal Antibody Targeting TauC3 Protein for the Treatment of Alzheimer’s Disease and Progressive Supranuclear Palsy

TAU BIO-LOGIC CORP. announced that, in collaboration with the UK-based group LifeArc, it has successfully humanized a monoclonal antibody (TBL-100) that targets C-terminally truncated tau (tauC3). TAU BIO-LOGIC is developing TBL-100 for the treatment of Alzheimer’s disease and progressive supranuclear palsy. [TAU BIO-LOGIC CORP.] Press Release

MediciNova Receives Notice of Allowance for New Patent Covering MN-166 (Ibudilast) for the Treatment of Glioblastoma

MediciNova, Inc. announced that it has received a Notice of Allowance from the US Patent and Trademark Office for a pending patent application which covers MN-166 for the treatment of glioblastoma. [MediciNova, Inc.] Press Release

FDA Hires Pew Director to Lead Regulatory Policy

Elizabeth Jungman, a well-known public health expert and a Capitol Hill veteran, will lead the FDA’s regulatory policy office starting this summer, STAT has learned. Jungman, who currently serves as head of public health programs at the Pew Charitable Trusts, will direct the FDA’s Office of Regulatory Policy, a post with sweeping authority over FDA’s human drugs portfolio, two sources told STAT. [STAT News] Editorial

After Firings, MD Anderson Officials Try to Calm Fears of Racial Profiling

Administrators at the MD Anderson Cancer Center in Houston, Texas, tried to reassure alarmed employees that its recent dismissals of faculty members alleged to have broken federal funding rules were not connected to race or ethnicity. [ScienceInsider] Editorial

NEW Keystone Symposia: Neurodegenerative Diseases: New Inisights and Therapeutic Opportunities
June 16-20, 2019
Keystone, Colorado, United States

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NEW Postdoctoral Positions – Astrocyte Research (Washington University in St.Louis)

Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

Postdoctoral Research Scientist – Systems Neuroscience (University of Oxford)

Postdoctoral Researcher – Neurobiological Mechanisms (Columbia University)

Senior Scientist – Tau Biology in Neuroscience Discovery (AbbVie Deutschland GmbH)

Postdoctoral Position – Retinal Stem Cell Biology (Johns Hopkins University)

Postdoctoral Fellow – Alcohol & Adult Neurogenesis (The University of Texas at Austin)

Postdoctoral Research Fellow – Neuroscience (The University of Texas at Austin)

Postdoctoral Researcher – Neurobiology (University of Rochester)

Staff Scientist – Molecular & Behavioral Neuroscience (Fred Hutchinson Cancer Research Center)

Postdoctoral Research Associate – Neurological Diseases (University of Utah)

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