Volume 7.10 | Mar 13

Neural Cell News 7.10 March 13, 2013
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CLP1 Links tRNA Metabolism to Progressive Motor-Neuron Loss
The authors generated kinase-dead Clp1 (Clp1K/K) mice that showed a progressive loss of spinal motor neurons associated with axonal degeneration in the peripheral nerves and denervation of neuromuscular junctions, resulting in impaired motor function, muscle weakness, paralysis and fatal respiratory failure. [Nature] Abstract | Press Release

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PUBLICATIONS (Ranked by impact factor of the journal)

Forebrain Engraftment by Human Glial Progenitor Cells Enhances Synaptic Plasticity and Learning in Adult Mice
To assess the cell-autonomous and species-selective properties of human glia, scientists engrafted human glial progenitor cells into neonatal immunodeficient mice. Upon maturation, the recipient brains exhibited large numbers and high proportions of both human glial progenitors and astrocytes. [Cell Stem Cell]
Full Article | Video Abstract | Press Release

Interplay of LRRK2 with Chaperone-Mediated Autophagy
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease. Researchers found LRRK2 to be degraded in lysosomes by chaperone-mediated autophagy, whereas the most common pathogenic mutant form of LRRK2, G2019S, was poorly degraded by this pathway. [Nat Neurosci] Abstract | Press Release

Aberrant Schwann Cell Lipid Metabolism Linked to Mitochondrial Deficits Leads to Axon Degeneration and Neuropathy
Researchers investigated a mouse model of peripheral neuropathy secondary to Schwann cell (SC) mitochondrial dysfunction. They showed that disruption of SC mitochondria activates a maladaptive integrated stress response through the actions of heme-regulated inhibitor kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. [Neuron] Abstract

Transient Treatment with Epigenetic Modifiers Yields Stable Neuroblastoma Stem Cells Resembling Aggressive Large-Cell Neuroblastomas
By treating neuroblastoma (NB) cell lines with epigenetic modifiers for a short time, followed by sphere-forming culture conditions, investigators have established stem cell-like NB cells that are phenotypically stable for more than a year. These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure. [Proc Natl Acad Sci USA] Full Article

TLR9 Mediates Cellular Protection by Modulating Energy Metabolism in Cardiomyocytes and Neurons
Scientists uncovered an unexpected role of toll-like receptor 9 (TLR9) in energy metabolism and cellular protection in cardiomyocytes and neurons. TLR9 stimulation reduced energy substrates and increased the AMP/ATP ratio, subsequently activating AMP-activated kinase, leading to increased stress tolerance against hypoxia in cardiomyocytes without inducing the canonical inflammatory response. [Proc Natl Acad Sci USA] Full Article

A Sympathetic Neuron Autonomous Role for Egr3-Mediated Gene Regulation in Dendrite Morphogenesis and Target Tissue Innervation
Scientists showed that Egr3 expression within sympathetic neurons is required for their normal innervation since isolated sympathetic neurons lacking Egr3 have neurite outgrowth abnormalities when treated with nerve growth factor and mice with sympathetic neuron-restricted Egr3 ablation have target tissue innervation abnormalities similar to mice lacking Egr3 in all tissues. [J Neurosci] Abstract

Minocycline Selectively Inhibits M1 Polarization of Microglia
Researchers used SOD1G93A mice as a model, which exhibit the motor neuron-specific neurodegenerative disease, amyotrophic lateral sclerosis. Administration of minocycline attenuated the induction of the expression of pro-inflammatory (M1) microglia markers during the progressive phase, whereas it did not affect the transient enhancement of expression of anti-inflammatory microglia markers during the early pathogenesis phase. [Cell Death Dis] Full Article

Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) Plays a Key Role in Vasculogenic Mimicry Formation, Neovascularization and Tumor Initiation by Glioma Stem-like Cells
The authors report a critical role of glioma stem-like cells (GSLCs) in the formation of vasculogenic mimicry (VM), which defines channels lined by tumor cells to supply nutrients to early growing tumors and tumor initiation. GSLCs preferentially expressed VEGFR-2 that upon activation by VEGF, mediated chemotaxis, tubule formation and increased expression of critical VM markers by GSLCs. [PLoS One] Full Article

Protection of Neuronal Diversity at the Expense of Neuronal Numbers during Nutrient Restriction in the Drosophila Visual System
In the Drosophila visual system, researchers identified two developmental phases with different sensitivities to dietary nutrients. During early larval stages, nutrients regulated the size of the neural progenitor pool via insulin/PI3K/TOR-dependent symmetric neuroepithelial divisions. [Cell Reports]
Full Article | Graphical Abstract

MiR-134 Regulates the Proliferation and Invasion of Glioblastoma Cells by Reducing Nanog Expression
Investigators defined the expression and function of miR-134, which they found to be downregulated in glioma samples and the glioblastoma cell line U87 by SYBR green real-time quantitative reverse transcription-PCR. [Int J Oncol] Abstract | Full Article

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Epigenetic Mechanisms in the Development and Maintenance of Dopaminergic Neurons
The authors review the epigenetic control of mesodiencephalic dopaminergic (mdDA) development, maturation and maintenance. As they highlight, epigenetic mechanisms play a pivotal role in all of these processes and the knowledge gathered from studying epigenetics in these contexts may aid our understanding of mdDA-related pathologies. [Development] Abstract
Proteostasis Therapeutics Presents Data at 11th International Conference on Alzheimer’s and Parkinson’s Diseases
Proteostasis Therapeutics, Inc., presented data supporting the Company’s protein clearance program in a poster titled “Developing Usp14 Inhibitors as Disease-Modifying Therapeutics for Protein Aggregation Diseases”. [Press release from Proteostasis Therapeutics, Inc. discussing research presented at the 11th International Conference on Alzheimer’s and Parkinson’s Diseases, Florence] Press Release

Merck and Luminex Corporation Enter Agreement to Develop Companion Diagnostic to Support Investigational BACE Inhibitor Clinical Development Program for Alzheimer’s Disease
Merck and Luminex Corporation have signed a collaboration and license agreement to develop a companion diagnostic device that will be evaluated to help screen patients for recruitment into Merck’s clinical development program for MK-8931, a novel oral beta amyloid precursor protein site cleaving enzyme (BACE) inhibitor and Merck’s lead investigational candidate for Alzheimer’s disease. [Merck & Co., Inc.]
Press Release

Human Connectome Project Releases Major Data Set on Brain Connectivity
The Human Connectome Project, a five-year endeavor to link brain connectivity to human behavior, has released a set of high-quality imaging and behavioral data to the scientific community. [NIH Blueprint for Neuroscience Research: The Human Connectome Project] Press Release


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