Volume 9.46 | Dec 9

Neural Cell News 9.46 December 9, 2015
Neural Cell News
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Brain-Borne IL-1 Adjusts Glucoregulation and Provides Fuel Support to Astrocytes and Neurons in an Autocrine/Paracrine Manner
Investigators showed that interleukin-1β (IL-1β) adjusts glucoregulation by inducing its own production in the brain, and that IL-1β-induced hypoglycemia is myeloid differentiation primary response 88 protein-dependent and only partially counteracted by Kir6.2-mediated sensing signaling. [Mol Psych] Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Aβ-Dependent Reduction of NCAM2-Mediated Synaptic Adhesion Contributes to Synapse Loss in Alzheimer’s Disease
The authors showed that the neural cell adhesion molecule 2 (NCAM2) is enriched in synapses in the human hippocampus. This enrichment is abolished in the hippocampus of AD patients and in brains of mice overexpressing the human amyloid-β (Aβ) precursor protein carrying the pathogenic Swedish mutation. Aβ binds to NCAM2 at the cell surface of cultured hippocampal neurons and induces removal of NCAM2 from synapses. [Nat Commun] Full Article | Press Release

PTEN Deficiency Reprograms Human Neural Stem Cells towards a Glioblastoma Stem Cell-Like Phenotype
Researchers showed that targeted disruption of PTEN leads to neoplastic transformation of human neural stem cells, but not mesenchymal stem cells. [Nat Commun] Full Article | Press Release

Mouse Models of Human PIK3CA-Related Brain Overgrowth Have Acutely Treatable Epilepsy
Researchers generated mouse models expressing the most common activating phosphoinositide 3-kinase (Pik3ca) mutations in developing neural progenitors. These accurately recapitulated all the key human pathological features including brain enlargement, cortical malformation, hydrocephalus and epilepsy, with phenotypic severity dependent on the mutant allele and its time of activation. [eLife]
Abstract | Full Article | Press Release

Cell Type-Dependent ROS and Mitophagy Response Leads to Apoptosis or Necroptosis in Neuroblastoma
Scientists investigated the molecular mechanisms by which the hemisynthetic cardiac glycoside UNBS1450 overcomes this limitation and induces differential cell death modalities in both neuroblastic and stromal neuroblastoma through stimulation of a cell-type-specific autophagic response eventually leading to apoptosis or necroptosis. [Oncogene] Abstract

Genome-Wide CRISPR-Cas9 Screens Reveal Loss of Redundancy between PKMYT1 and WEE1 in Glioblastoma Stem-Like Cells
To identify therapeutic targets for glioblastoma (GBM), the authors performed genome-wide CRISPR-Cas9 knockout screens in patient-derived GBM stem-like cells and human neural stem/progenitors, non-neoplastic stem cell controls, for genes required for their in vitro growth. [Cell Rep] Full Article | Graphical Abstract

Learning-Induced Synaptic Potentiation in Implanted Neural Precursor Cell-Derived Neurons
Scientists characterized the functional properties of immortalized neural progenitor HiB5 cells implanted into the rat hippocampus with chemically induced lesion. [Sci Rep] Full Article

Burst Predicting Neurons Survive an In Vitro Glutamate Injury Model of Cerebral Ischemia
Scientists examined the role of burst predictors in cultures undergoing an in vitro model of cerebral ischemia. Dissociated primary cortical neurons were plated on multielectrode arrays and spontaneous activity was recorded at 17 days in vitro. [Sci Rep] Full Article

Synthetic and Natural Small Molecule TLR4 Antagonists Inhibit Motoneuron Death in Cultures from ALS Mouse Model
Toll-like receptor 4 (TLR4) antagonists efficiently protected motoneurons from LPS-induced lethality in spinal cord cultures, and inhibited the interleukin-1β production by LPS-stimulated microglia. [Pharmacol Res] Abstract

Hippocampal Neurogenesis in the APP/PS1/Nestin-GFP Triple Transgenic Mouse Model of Alzheimer’s Disease
To assess the relationship between Alzheimer’s disease (AD) and neurogenesis, researchers studied APP/PS1/nestin-green fluorescent protein (GFP) triple transgenic mice, a well-characterized mouse model of AD, which express GFP under the control of the nestin promoter. [Neuroscience] Abstract

The Synergistic Local Immunosuppressive Effects of Neural Stem Cells Expressing Indoleamine 2,3-Dioxygenase (IDO) in an Experimental Autoimmune Encephalomyelitis (EAE) Animal Model
The synergistic immune suppressive effects of rat fetal neural stem cells expressing IDO were validated by mixed leukocyte reaction in vitro and an EAE animal model in vivo. [PLoS One] Full Article

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WNT Signaling in Glioblastoma and Therapeutic Opportunities
The authors summarize the experimental evidence supporting oncogenic roles of WNT signaling in glioblastoma and discuss current progress in the targeting of WNT signaling as an anti-cancer approach. [Lab Invest] Full Article

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ImmunoCellular Therapeutics Establishes Agreement with Alliance Foundation Trials, LLC for ICT-107 Phase III Registrational Trial in Glioblastoma
ImmunoCellular Therapeutics, Ltd. announced the establishment of an agreement with a major cancer research group, Alliance Foundation Trials, LLC, for the Phase III registrational trial of its cancer immunotherapy ICT-107 in patients with newly diagnosed glioblastoma. [ImmunoCellular Therapeutics, Ltd.] Press Release

First Patient Enrolled in Toca 5, Tocagen’s Phase II/III Clinical Trial in Patients with Recurrent Glioblastoma or Anaplastic Astrocytoma
Tocagen Inc. announced that the first patient has been enrolled in the Phase II portion of its randomized, controlled Phase II/III clinical trial of Toca 511 & Toca FC against current standard of care in patients with first or second recurrence of glioblastoma or anaplastic astrocytoma who are undergoing resection. [Tocagen Inc.] Press Release

Tetra Discovery Initiates Phase I Study of BPN14770, under Development for Treatment and Prevention of Alzheimer’s Disease
Tetra Discovery Partners announced that the company has initiated human Phase I safety trials of its lead compound BPN14770, which Tetra is developing as a potential treatment to both improve memory and slow the progression of Alzheimer’s disease. [Tetra Discovery (PR Newswire Association LLC)] Press Release

UC San Diego Receives Michael J. Fox Foundation Grant to Identify Parkinson’s Biomarkers
Parkinson’s disease is difficult to diagnose, particularly in its early stages. Now, researchers at University of California, San Diego School of Medicine – aided by a $375,000 grant from The Michael J. Fox Foundation for Parkinson’s Research – hope to improve the prospects of early diagnosis by identifying a biological signpost in the blood. [University of California, San Diego School of Medicine] Press Release

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