Neural Cell News Volume 7.06 | Feb 13 2013

Loss of Dickkopf-1 Restores Neurogenesis in Old Age and Counteracts Cognitive Decline
Researchers showed that expression of the Wnt antagonist Dickkopf-1 (Dkk1) increases with age and that its loss enhances neurogenesis in the hippocampus. Neural progenitors with inducible loss of Dkk1 increase their Wnt activity, which leads to enhanced self-renewal and increased generation of immature neurons. [Cell Stem Cell] Abstract | Graphical Abstract

Pyramidal Neurons Derived from Human Pluripotent Stem Cells Integrate Efficiently into Mouse Brain Circuits In Vivo
Investigators found that human embryonic stem cells and induced pluripotent stem cells, cultured without added morphogens, recapitulate corticogenesis leading to the sequential generation of functional pyramidal neurons of all six layer identities. [Neuron] Abstract | Video Abstract

TRAK/Milton Motor-Adaptor Proteins Steer Mitochondrial Trafficking to Axons and Dendrites
Researchers showed that TRAK family adaptor proteins, TRAK1 and TRAK2, which link mitochondria to microtubule-based motors, are required for axonal and dendritic mitochondrial motility and utilize different transport machineries to steer mitochondria into axons and dendrites. [Neuron] Abstract

Astrocyte Pathology and the Absence of Non-Cell Autonomy in an Induced Pluripotent Stem Cell Model of TDP-43 Proteinopathy
Investigators generated functional astroglia from human induced pluripotent stem cells carrying an amyotrophic lateral sclerosis (ALS)-causing transactive response DNA-binding protein (TDP-43) mutation and showed that mutant astrocytes exhibit increased levels of TDP-43, subcellular mislocalization of TDP-43, and decreased cell survival. [Proc Natl Acad Sci USA] Abstract | Full Article | Press Release

Neto2 Is a KCC2 Interacting Protein Required for Neuronal Cl⁻ Regulation in Hippocampal Neurons
Scientists showed that KCC2 is critically regulated by the single-pass transmembrane protein neuropilin and tolloid like-2 (Neto2). Neto2 is required to maintain the normal abundance of KCC2 and specifically associates with the active oligomeric form of the transporter. [Proc Natl Acad Sci USA] Abstract

Elevated Id2 Expression Results in Precocious Neural Stem Cell Depletion and Abnormal Brain Development
The authors report that analyses of Id2 transgenic brains indicate that Id2 activity is highly cell context specific: elevated Id2 expression in naive neural stem cells (NSCs) in early neuroepithelium induces apoptosis and loss of NSCs and intermediate progenitors. [Stem Cells] Abstract

Cytotoxicity of Botulinum Neurotoxins Reveals a Direct Role of Syntaxin 1 and SNAP-25 in Neuron Survival
Scientists report that cleavage of syntaxin 1 by botulinum neurotoxins (BoNT)/C, and cleavage of SNAP-25 by BoNT/E both induce degeneration of neurons. [Nat Commun] Abstract

NF-κB Forms a Complex with the Chromatin Remodeler BRG1 to Regulate Schwann Cell Differentiation
Scientists report that BRG1/SMARCA4, the central helicase of the mammalian SWI/SNF-related chromatin remodeling complex, is required for Schwann cells to differentiate and form myelin, both in vitro and in vivo, in the mouse. [J Neurosci] Abstract

RNAi-Mediated Stathmin Suppression Reduces Lung Metastasis in an Orthotopic Neuroblastoma Mouse Model
Scientists investigated stathmin’s contribution to neuroblastoma tumor growth and metastasis. Small interfering RNA (siRNA)-mediated stathmin suppression in two independent neuroblastoma cell lines, BE(2)-C and SH-SY5Y, did not markedly influence cell proliferation, viability or anchorage-independent growth. [Oncogene] Abstract

Hepatocyte Growth Factor Activator Inhibitor-1 Is Induced by Bone Morphogenetic Proteins and Regulates Proliferation and Cell Fate of Neural Progenitor Cells
Investigators showed that the cell-surface serine protease inhibitors hepatocyte growth factor activator inhibitor-1 and -2 influence proliferation and cell fate of neural progenitor cells, and their expression levels are linked to bone morphogenetic protein signaling. [PLoS One] Full Article

Metabolic Solutions Development Company Awarded Funding by The Michael J. Fox Foundation
Metabolic Solutions Development Company, LLC., announced that it has received an award from The Michael J. Fox Foundation for Parkinson’s Research to conduct preclinical research on a first-in-class mTOT Modulator, MSDC-0160, as a potential treatment for levodopa induced dyskinesia. [Metabolic Solutions Development Company, LLC.] Press Release

Lentigen Receives U.S. Orphan Drug Designation for Novel Gene Therapy for Glioblastoma Multiforme
Lentigen Corporation, a biotechnology company specializing in the development and manufacture of lentiviral gene delivery products, announced that the U.S. Food and Drug Administration has granted orphan drug status to P140K methylguanine methyltransferase transduced human CD34 cells for bone marrow protection in the treatment of glioblastoma multiforme. [PR NewsWire Association LLC.] Press Release

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