Neural Cell News Volume 7.15 | Apr 17 2013

Transcription Factor-Mediated Reprogramming of Fibroblasts to Expandable, Myelinogenic Oligodendrocyte Progenitor Cells
Investigators describe direct conversion of mouse embryonic and lung fibroblasts to induced oligodendrocyte progenitor cells (iOPCs) using sets of either eight or three defined transcription factors. When transplanted to hypomyelinated mice, iOPCs are capable of ensheathing host axons and generating compact myelin. [Nat Biotechnol] Abstract | Press Release

Generation of Oligodendroglial Cells by Direct Lineage Conversion
Scientists report the generation of induced oligodendrocyte precursor cells (iOPCs) by direct lineage conversion. Forced expression of the three transcription factors Sox10, Olig2 and Zfp536 was sufficient to reprogram mouse and rat fibroblasts into iOPCs with morphologies and gene expression signatures resembling primary OPCs. [Nat Biotechnol] Abstract | Press Release

The CAMKK2-AMPK Kinase Pathway Mediates the Synaptotoxic Effects of Aβ Oligomers through Tau Phosphorylation
Scientists showed that increased intracellular calcium [Ca²⁺]_i induced by NMDA receptor activation or membrane depolarization activates AMP-activated kinase (AMPK) in a CAMKK2-dependent manner. CAMKK2 or AMPK overactivation is sufficient to induce dendritic spine loss. Conversely, inhibiting their activity protects hippocampal neurons against synaptotoxic effects of amyloid-β 1-42 (Aβ42) oligomers in vitro and against the loss of dendritic spines observed in the human APP^SWE,IND-expressing transgenic mouse model in vivo. [Neuron] Abstract | Press Release

Transglutaminase and Polyamination of Tubulin: Posttranslational Modification for Stabilizing Axonal Microtubules
Researchers showed that neuronal tubulin can be polyaminated by transglutaminase. Endogenous brain transglutaminase-catalyzed polyaminated tubulins have the biochemical characteristics of neuronal stable microtubules. Inhibiting polyamine synthesis or transglutaminase activity significantly decreases microtubule stability in vitro and in vivo. [Neuron] Abstract | Press Release

Exosomes Reflect the Hypoxic Status of Glioma Cells and Mediate Hypoxia-Dependent Activation of Vascular Cells during Tumor Development
Scientists showed that secreted vesicles with exosome characteristics mediate hypoxia-dependent intercellular signaling of the highly malignant brain tumor glioblastoma multiforme. In vitro hypoxia experiments with glioma cells and studies with patient materials reveal the enrichment in exosomes of hypoxia-regulated mRNAs and proteins, several of which were associated with poor glioma patient prognosis. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

The Transcription Factor Hmx1 and Growth Factor Receptor Activities Control Sympathetic Neurons Diversification
The sympathetic nervous system relies on distinct populations of neurons that use noradrenaline or acetylcholine as neurotransmitter. Researchers showed that fating of the sympathetic lineage at early stages results in hybrid precursors from which, genetic cell-lineage tracing reveals, all types progressively emerge by principal mechanisms of maintenance, repression and induction of phenotypes. [EMBO J] Abstract

p38MAPK Inhibition: A New Combined Approach to Reduce Neuroblastoma Resistance under Etoposide Treatment
This study was carried out on three stage-IV neuroblastoma cell lines with different status of MYCN amplification. Cells were exposed to a standard chemotherapy agent, namely etoposide, either alone or in combination with particular drugs, which target intracellular signaling pathways. Scientists report that etoposide alone induced a concentration-dependent reduction of cell viability and, at very high doses, totally counteracted cell tumorigenicity and neurosphere formation. [Cell Death Dis] Full Article

Fingolimod Phosphate Attenuates Oligomeric Amyloid β-Induced Neurotoxicity via Increased Brain-Derived Neurotrophic Factor Expression in Neurons
Researchers showed that the sphingosine-1-phosphate (S1P) receptor agonist fingolimod phosphate (FTY720-P)-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. They confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. [PLoS One] Full Article

Mitotic Spindle Defects and Chromosome Mis-Segregation Induced by LDL/Cholesterol-Implications for Niemann-Pick C1, Alzheimer’s Disease, and Atherosclerosis
Scientists tested the hypothesis that, like upregulated Aß, elevated low-density lipoprotein (LDL)/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. They found that Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans. [PLoS One] Full Article

Acute Stress Enhances Adult Rat Hippocampal Neurogenesis and Activation of Newborn Neurons via Secreted Astrocytic FGF2
Investigators found that acute stress increased hippocampal cell proliferation and astrocytic fibroblast growth factor 2 (FGF2) expression. The effect of acute stress occurred independent of basolateral amygdala neural input and was mimicked by treating isolated neural stem/progenitor cells with conditioned media from corticosterone-treated primary astrocytes. [eLife] Full Article | Press Release

Towards Clinical Application of Mesenchymal Stem Cells for Treatment of Neurological Diseases of the Central Nervous System
The authors review the therapeutic features of mesenchymal stem cells (MSC) that make them relevant in the treatment of central nervous system illnesses and discuss the pioneer clinical experience with MSC-based therapy in neurological diseases. [J Neuroimmune Pharm] Abstract

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StemCells, Inc. Enters Agreement to Receive $19.3 Million from California Institute for Regenerative Medicine to Help Fund IND for Alzheimer’s Disease
StemCells, Inc. announced that it has entered into an agreement with the California Institute for Regenerative Medicine under which CIRM will provide approximately $19.3 million to help fund preclinical development and IND-enabling activities of the Company’s proprietary HuCNS-SC® product candidate (purified human neural stem cells) for Alzheimer’s disease. [StemCells, Inc.] Press Release

Neuralstem Receives FDA Approval to Commence Phase II Stem Cell Trial in Amytrophic Lateral Sclerosis
Neuralstem, Inc. announced that it has received approval from the Food and Drug Administration to commence a Phase II trial using NSI-566 spinal cord-derived human neural stem cells in the treatment of amyotrophic lateral sclerosis. [Neuralstem, Inc.] Press Release

WomenAgainstAlzheimer’s Launches To Bring New Urgency To Ending Alzheimer’s
USAgainstAlzheimer’s-the national community and movement committed to stopping Alzheimer’s by 2020-launched WomenAgainstAlzheimer’s, the first national network of women in leadership positions working to speed the pace of research and build real momentum to end Alzheimer’s disease. [US Against Alzheimer’s] Press Release

HHMI Announces $65 Million in Grants for Research Universities
The Howard Hughes Medical Institute (HHMI) is announcing a new round of science education grants aimed at helping research universities improve persistence of students studying STEM disciplines and reinvigorating introductory science courses. [Howard Hughes Medical Institute] Press Release

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