Volume 7.11 | Mar 20

Neural Cell News 7.11 March 20, 2013
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Opposing Regulation of Sox2 by Cell-Cycle Effectors E2f3a and E2f3b in Neural Stem Cells
Investigators showed that E2f3 isoforms, which control cell-cycle progression in cooperation with the retinoblastoma protein, have critical effects during developmental and adult neurogenesis. Loss of either E2f3 isoform disrupts Sox2 gene regulation and the balance between precursor maintenance and differentiation in the developing cortex. [Cell Stem Cell] Abstract | Graphical Abstract

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Local Potentiation of Excitatory Synapses by Serotonin and Its Alteration in Rodent Models of Depression
Scientists found that endogenous serotonin selectively potentiated excitatory synapses formed by the temporoammonic pathway with CA1 pyramidal cells via activation of serotonin receptors, without affecting nearby Schaffer collateral synapses. [Nat Neurosci] Abstract | Press Release

β-Tubulin Mutations that Cause Severe Neuropathies Disrupt Axonal Transport
Investigators have analyzed β-tubulin mutations that cause neuronal diseases and they identified mutations that strongly inhibited axonal transport of vesicles and mitochondria. [EMBO J] Abstract

SPARC Regulates Microgliosis and Functional Recovery following Cortical Ischemia
Investigators report that after photothrombotic stroke in the forelimb sensorimotor cortex, secreted protein acidic rich in cysteine (SPARC) nulls demonstrate enhanced microgliosis in and around the lesion site, which accompanies significantly enhanced functional recovery by 32 days after lesion. Microglia from SPARC nulls also intrinsically proliferate at a greater rate in vitro: an enhanced effect that can be rescued by the addition of exogenous SPARC. [J Neurosci] Abstract

Novel HSP90 Inhibitor NVP-HSP990 Targets Cell Cycle Regulators to Ablate Olig2-Positive Glioma Tumor Initiating Cells
Investigators evaluated the effects of a novel HSP90 inhibitor, NVP-HSP990, in glioma tumor initiating cell (GIC) populations, which are strongly implicated in the root pathobiology of glioblastoma multiforme. In GIC cultures, NVP-HSP990 elicited a dose-dependent growth inhibition with IC50 values in the low nanomolar range. [Cancer Res] Abstract

Developing Rods Transplanted into the Degenerating Retina of Crx-Knockout Mice Exhibit Neural Activity Similar to Native Photoreceptors
Researchers described the physiological properties of developing rod photoreceptors that are tagged with GFP driven by the promoter of rod differentiation factor, Nrl. GFP-tagged developing rods show Ca2+ responses and rectifier outward currents that are smaller than those observed in fully developed photoreceptors, suggesting their immature developmental state. [Stem Cells] Abstract

Derivation of Sensory Neurons and Neural Crest Stem Cells from Human Neural Progenitor hNP1
The authors report the differentiation of sensory neurons from a human neural progenitor cell line, hNP1, and their functional maturation in a defined, in vitro culture system without murine cell feeder layers. [Biomaterials] Abstract

BACE1 and Presenilin/γ-Secretase Regulate Proteolytic Processing of KCNE1 and 2, Auxiliary Subunits of Voltage-Gated Potassium Channels
Scientists report that KCNE1 and KCNE2, auxiliary subunits of voltage-gated potassium channels, undergo sequential cleavage mediated by either α-secretase and presenilin (PS)/γ-secretase or BACE1 and PS/γ-secretase in cells. Elevated α-secretase or BACE1 activities increased C-terminal fragment levels of KCNE1 and 2 in human embryonic kidney and rat neuroblastoma cells. [FASEB J] Abstract

Calsyntenin-3 C-Terminal Fragment Accumulates in Dystrophic Neurites Surrounding Aβ Plaques in Tg2576 Mouse and Alzheimer Disease Brains: Its Neurotoxic Role in Mediating Dystrophic Neurite Formation
Researchers showed that the CTF but not full-length calsyntenin-3 (Cst-3) accumulated in dystrophic neurites surrounding β-amyloid (Aβ) plaques in Tg2576 mouse and Alzheimer disease-affected brain. In vitro experiments with Cst-3 fragments revealed that only the CTF resulted in acceleration of neuronal death. [Am J Pathol] Abstract

Induced Pluripotent Stem Cell-Derived Neural Cells Survive and Mature in the Nonhuman Primate Brain
Investigators showed that transplanted autologous rhesus monkey induced pluripotent stem cell-derived neural progenitors survive for up to six months and differentiate into neurons, astrocytes, and myelinating oligodendrocytes in the brains of MPTP-induced hemiparkinsonian rhesus monkeys with a minimal presence of inflammatory cells and reactive glia. [Cell Rep] AbstractGraphical Abstract | Press Release

Deriving Dopaminergic Neurons for Clinical Use. A Practical Approach
New small molecules that regulate the step-wise differentiation of human pluripotent stem cells into dopaminergic neurons have been identified. The steroid, guggulsterone, was found to be the most effective inducer of neural stem cells into dopaminergic neurons. [Sci Rep] Full Article | Press Release

Webinar: Brent Reynolds on Identification and Characterization of Neural Stem Cells

Neurons as Targets for T Cells in the Nervous System
The authors review the modalities of neuron/T cell interactions. They substantiate the contention that T cells are directly responsible for neuronal damage in a large number of neurological diseases and discuss mechanisms of neuronal damage mediated by distinct T cell subsets, the impact of which differs depending on the disease. Finally, they describe how a better understanding of the mechanisms at play offers new possibilities for therapeutic intervention. [Trends Neurosci] Abstract

Translational CNS Summit

FDA Grants TransTech Pharma Inc. Fast Track Designation for TTP488 for the Treatment of Alzheimer’s Disease
TransTech Pharma Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for TTP488, a new small-molecule chemical compound being developed for the treatment of Alzheimer’s disease. TTP488 prevents the interaction of amyloid beta, a material found in the cells of Alzheimer’s patients, and a member of the immunoglobulin supergene family of molecules known as the Receptor for Advanced Glycation Endproducts. [Business Wire] Press Release

New Alzheimer’s Association Report Reveals 1 in 3 Seniors Dies with Alzheimer’s or Another Dementia
According to the Alzheimer’s Association 2013 Alzheimer’s Disease Facts and Figures report, one in three seniors dies with Alzheimer’s or another dementia in the United States. The new report shows that while deaths from other major diseases, such as heart disease, HIV/AIDS and stroke, continue to experience significant declines, Alzheimer’s deaths continue to rise – increasing 68 percent from 2000-2010. [Alzheimer’s Association] Press Release


National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

NEW European Stroke Conference
May 28-31, 2013
London, United Kingdom

Visit our events page to see a complete list of events in the neural cell community.

Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

Postdoctoral Fellow – Neural Stem Cells and Neurogenesis (UT Southwestern Medical Center)

Lecturer or Reader – Associate Professor (University of Reading)

Postdoctoral Position – Adult Neurogenesis and Neural Survival Signaling (University of Kentucky)

Postdoctoral Fellow – Regulation of Gliomagenesis (UT Southwestern Medical Center at Dallas)

PhD Opportunity (University of East Anglia)

Chief Laboratory Scientist – Cell Culture Specialist (Axol Bioscience Ltd)

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