Neural Cell News Volume 7.17 | May 1 2013

Integrated Systems Approach Identifies Genetic Nodes and Networks in Late-Onset Alzheimer’s Disease
To characterize molecular systems associated with late-onset Alzheimer’s disease (LOAD), scientists constructed gene-regulatory networks in 1,647 postmortem brain tissues from LOAD patients and nondemented subjects, and they demonstrate that LOAD reconfigures specific portions of the molecular interaction structure. Mouse microglia cells overexpressing intact or truncated TYROBP revealed expression changes that significantly overlapped the human brain TYROBP network. [Cell]
Abstract | Graphical Abstract | Full Article | Press Release

Trnp1 Regulates Expansion and Folding of the Mammalian Cerebral Cortex by Control of Radial Glial Fate
Researchers identified the DNA-associated protein Trnp1 as a regulator of cerebral cortex expansion in both of these dimensions. Gain- and loss-of-function experiments in the mouse cerebral cortex in vivo demonstrate that high Trnp1 levels promote neural stem cell self-renewal and tangential expansion. [Cell] Abstract | Graphical Abstract | Press Release

PINK1-Phosphorylated Mitofusin 2 Is a Parkin Receptor for Culling Damaged Mitochondria
Investigators showed that the mitochondrial outer membrane guanosine triphosphatase mitofusin (Mfn) 2 mediates Parkin recruitment to damaged mitochondria. Parkin bound to Mfn2 in a phosphatase and tensin homolog-induced putative kinase protein 1 (PINK1)-dependent manner; PINK1 phosphorylated Mfn2 and promoted its Parkin-mediated ubiqitination. [Science] Abstract | Press Release

Alzheimer’s Disease Risk Gene CD33 Inhibits Microglial Uptake of Amyloid Beta
Scientists observed increased expression of CD33 in microglial cells in Alzheimer’s disease (AD) brain. The minor allele of the CD33 SNP rs3865444, which confers protection against AD, was associated with reductions in both CD33 expression and insoluble amyloid beta 42 levels in AD brain. [Neuron]
Abstract | Full Article | Press Release

Modulation of the Endoplasmic Reticulum-Mitochondria Interface in Alzheimer’s Disease and Related Models
Scientists studied endoplasmic reticulum (ER)-mitochondria contacts in human Alzheimer’s disease (AD) brain and related AD mouse and neuronal cell models. They found uniform distribution of mitochondria-associated ER membranes (MAM) in neurons. Phosphofurin acidic cluster sorting protein-2 and σ1 receptor, two MAM-associated proteins, were shown to be essential for neuronal survival, because siRNA knockdown resulted in degeneration. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

CD133 Is Essential for Glioblastoma Stem Cell Maintenance
Investigators studied the biological effects of CD133 downregulation in glioblastoma patient-derived neurospheres. Their results indicate that there is not a hierarchical relation between CD133-positive and CD133-negative cells composing the neurospheres. [Stem Cells] Abstract | Full Article

Tumor-Specific Activation of the C-JUN/MELK Pathway Regulates Glioma Stem Cell Growth in a p53-Dependent Manner
Scientists demonstrated that maternal embryonic leucine-zipper kinase (MELK) depletion by shRNA diminishes the growth of glioma stem cell (GSC)-derived mouse intracranial tumors in vivo, induces glial fibrillary acidic protein (+) glial differentiation of GSCs leading to decreased malignancy of the resulting tumors, and prolongs survival periods of tumor-bearing mice. [Stem Cells] Abstract | Full Article

Visualization and Genetic Modification of Resident Brain Microglia Using Lentiviral Vectors Regulated by MicroRNA-9
Using transgenic reporter mice, investigators demonstrated that murine microglia lack microRNA-9 activity, whereas most other cells in the brain express microRNA-9. Injection of microRNA-9-regulated vectors into the adult rat brain induces transgene expression specifically in cells with morphological features typical of ramified microglia. [Nat Commun] Abstract | Press Release

Alpha-Synuclein Induces Lysosomal Rupture and Cathepsin Dependent Reactive Oxygen Species following Endocytosis
Recent studies of viruses and bacteria, which achieve their cytoplasmic entry by rupturing intracellular vesicles, have utilized the redistribution of galectin proteins as a tool to measure vesicle rupture by these organisms. Using this approach, researchers demonstrated that α-synuclein aggregates can induce the rupture of lysosomes following their endocytosis in neuronal cell lines. [PLoS One]
Full Article | Press Release

MicroRNA Cluster miR-17-92 Regulates Neural Stem Cell Expansion and Transition to Intermediate Progenitors in the Developing Mouse Neocortex
The authors demonstrated that the microRNA (miRNA) miR-17-92 cluster is required for maintaining proper populations of cortical radial glial cells (RGCs) and intermediate progenitors (IPs) through repression of Pten and Tbr2 protein. Knockout of miR-17-92 and its paralogs specifically in the developing neocortex restricts neural stem cells proliferation, suppresses RGC expansion, and promotes transition of RGCs to IPs. [Cell Rep] Abstract | Graphical Abstract | Full Article

Autophagy in Axonal and Dendritic Degeneration
Emerging evidence shows that insufficient or excessive autophagy contributes to neuritic degeneration. The authors review the recent progress that has begun to reveal the role of autophagy in neurite function and degeneration. [Trends Neurosci] Abstract

Visit our reviews page to see a complete list of reviews in the neuroscience field.

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Afraxis, Inc. and Servier Announce a Collaboration on ESP Platform for Drug Discovery in Central Nervous System Disorders
Afraxis, Inc. and Institut de Recherches Servier announced a non-exclusive platform collaboration using Afraxis’ Enhanced Spine Platform (ESP) Technology for the discovery of drugs to treat central nervous system disorders. [Servier] Press Release

Neuralstem and the National Football League Alumni Association Announce Initiative on Brain Injury Treatment
Neuralstem, Inc. announced that it is working with the National Football League Alumni Association, based in Newark, NJ, to develop a trial for treating NFL alumni members suffering from traumatic brain injuries, with NSI-189, the lead compound in the company’s neurogenic drug platform. [Neuralstem Inc.]
Press Release

STEMCELL Technologies Inc. Obtains License from iPS Academia Japan for Induced Pluripotent Stem Cell Technologies
STEMCELL Technologies Inc. has signed an agreement to license iPS Academia Japan’s induced pluripotent stem cell (iPS cell) technologies. This agreement will enable STEMCELL Technologies to develop media that are optimized for cellular reprogramming, further expanding its extensive portfolio of products designed to facilitate cutting-edge pluripotent stem cell research. [STEMCELL Technologies Inc.] Press Release

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NEW Research Fellow – Neural Stem Cells/Neurogenesis (Ikerbasque, the Basque Foundation for Science)

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Postdoctoral Position – Neurobiology (Weizmann Institute of Science)

PhD Opportunity – Role of Fibroblast Growth Factors in the Generation of Neuronal Diversity in the Spinal Cord (University of East Anglia)

Doctoral Studentship – Neural Cell Physiology (CNR-ISMN)

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