Neural Cell News Volume 6.25 | Jun 27 2012

Sustained Therapeutic Reversal of Huntington’s Disease by Transient Repression of Huntingtin Synthesis
With antisense oligonucleotides that catalyze RNase H-mediated degradation of huntingtin mRNA, scientists demonstrated that transient infusion into the cerebrospinal fluid of symptomatic Huntington’s disease mouse models not only delays disease progression but mediates a sustained reversal of disease phenotype that persists longer than the huntingtin knockdown. [Neuron] Abstract | Press Release

Dual Leucine Zipper Kinase Is Required for Retrograde Injury Signaling and Axonal Regeneration
The authors demonstrated that the dual leucine zipper kinase promotes robust regeneration of peripheral axons after nerve injury in mice. [Neuron] Abstract | Press Release

Dynamic FoxG1 Expression Coordinates the Integration of Multipolar Pyramidal Neuron Precursors into the Cortical Plate
By utilizing conditional genetic strategies, researchers showed that the downregulation of FoxG1 at the beginning of the multipolar cell phase induces Unc5D expression, the timing of which ultimately determines the laminar identity of pyramidal neurons. [Neuron] Abstract

Axon Injury and Stress Trigger a Microtubule-Based Neuroprotective Pathway
Researchers found that increased microtubule dynamics can delay short-term injury-induced degeneration, and, in the case of poly-Q proteins, can counteract progressive longer-term degeneration. They concluded that axon injury or stress triggers a microtubule-based neuroprotective pathway that stabilizes neurons against degeneration. [Proc Natl Acad Sci USA] Abstract

Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells
Researchers showed that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells. [Cancer Res] Abstract

RBFOX1 Regulates Both Splicing and Transcriptional Networks in Human Neuronal Development
Scientists used RNA sequencing to identify the RNA-binding protein, fox-1 (RBFOX1) splicing network at a genome-wide level in primary human neural stem cells during differentiation. They observed that RBFOX1 regulates a wide range of alternative splicing events implicated in neuronal development and maturation, including transcription factors, other splicing factors, and synaptic proteins. [Hum Mol Genet] Abstract

A Drosophila Model of Spinal Muscular Atrophy Uncouples snRNP Biogenesis Functions of Survival Motor Neuron from Locomotion and Viability Defects
The spinal muscular atrophy protein, survival motor neuron (SMN), functions in the biogenesis of small nuclear ribonucleoproteins (snRNP). Smn null mutants display larval lethality and show significant locomotion defects as well as reductions in minor-class spliceosomal snRNAs. Despite these reductions, researchers found no appreciable defects in the splicing of mRNAs containing minor-class introns. [Cell Reports] Abstract | Press Release

Coordination between Proteasome Impairment and Caspase Activation Leading to TAU Pathology: Neuroprotection by cAMP
Researchers demonstrated that upon proteasome inhibition, the early accumulation of detergent-soluble ubiquitinated proteins paves the way to caspase activation and TAU pathology. This occurs with two drugs that inhibit the proteasome by different means: the product of inflammation prostaglandin J2 and epoxomicin. [Cell Death Dis] Abstract

Constitutive Notch2 Signaling in Neural Stem Cells Promotes Tumorigenic Features and Astroglial Lineage Entry
Researchers demonstrated that mice constitutively expressing the activated intracellular domain of Notch2 in neural stem cells display a hyperplasia of the neurogenic niche and reduced neuronal lineage entry. Neurospheres derived from these mice show increased proliferation, survival and resistance to apoptosis. [Cell Death Dis] Abstract

Miami Children’s Hospital Performs First Nerve Repair Surgery Using Avance Nerve® Graft Technology
Miami Children’s Hospital announced the hospital’s first nerve repair surgery with Avance® Nerve Graft. The processed nerve allograft technology was implanted during a surgery recently to repair a brachial plexus injury suffered by a six month-old baby girl. [Miami Children’s Hospital] Press Release

uniQure Collaborates with University of California, San Francisco, on GDNF Gene Therapy in Parkinson’s Disease
uniQure announced the signing of a collaborative agreement with two leading neurology experts to develop further a gene therapy incorporating uniQure’s GDNF (glial cell derived neurotrophic factor) gene for the treatment of Parkinson’s disease. [uniQure] Press Release

First Patients Dosed in Ib Phase of Neuralstem’s NSI-189 Trial in Major Depressive Disorder
Neuralstem, Inc. announced that the first patients were dosed in Phase Ib of its ongoing trial to test the safety of NSI-189 in the treatment of major depressive disorder (MDD). [Neuralstem, Inc.] Press Release

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