Neural Cell News 11.06 February 15, 2017 | |
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TOP STORYThe authors demonstrated editing of post-mitotic neurons in the adult mouse brain following injection of Cas9 ribonucleoprotein complexes in the hippocampus, striatum and cortex. Engineered variants of Cas9 with multiple SV40 nuclear localization sequences enabled a tenfold increase in the efficiency of neuronal editing in vivo. [Nat Biotechnol] Abstract | |
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PUBLICATIONS(Ranked by impact factor of the journal)C. elegans Neurons Jettison Protein Aggregates and Mitochondria under Neurotoxic Stress Investigators showed that adult neurons from Caenorhabditis elegans extrude large membrane-surrounded vesicles called exophers that can contain protein aggregates and organelles. Inhibition of chaperone expression, autophagy or the proteasome, in addition to compromising mitochondrial quality, enhances the production of exophers. Proteotoxically stressed neurons that generate exophers subsequently function better than similarly stressed neurons that did not produce exophers. [Nature] Abstract | Press Release G1 Cyclins Link Proliferation, Pluripotency and Differentiation of Embryonic Stem Cells Researchers showed that several cell types can proliferate in the absence of all G1 cyclins. However, following ablation of G1 cyclins, embryonic stem cells attenuated their pluripotent characteristics, with the majority of cells acquiring the trophectodermal cell fate. They established that G1 cyclins, together with their associated cyclin-dependent kinases, phosphorylate and stabilize the core pluripotency factors Nanog, Sox2 and Oct4. [Nat Cell Biol] Abstract AKAP-Mediated Feedback Control of cAMP Gradients in Developing Hippocampal Neurons Investigators revealed that cyclic AMP (cAMP) forms a gradient in developing hippocampal neurons, with higher cAMP levels in more distal regions of the axon compared to other regions of the cell. Interestingly, this cAMP gradient changed according to the developmental stage and depended on proper anchoring of protein kinase A (PKA) by A-kinase anchoring proteins (AKAPs). Disrupting PKA anchoring to AKAPs increased the cAMP gradient in early-stage neurons and led to enhanced axon elongation. [Nat Chem Biol] Abstract The authors report that heat shock transcription factor 1 (HSF1) is degraded in cells and mice expressing mutant Htt, in medium spiny neurons derived from human Huntington’s Disease (HD) iPSCs and in brain samples from patients with HD. [Nat Commun] Full Article | Press Release Spinal muscular atrophy severity inversely correlates with the copy number of Survival Motor Neuron 2 (SMN2), a duplicated gene that is nearly identical to SMN1. Scientists have delineated a mechanism of transcriptional regulation in the SMN2 locus. A previously uncharacterized long noncoding RNA (lncRNA), SMN-antisense 1, represses SMN2 expression by recruiting the Polycomb Repressive Complex 2 (PRC2) to its locus. [Proc Natl Acad Sci USA] Full Article Researchers constructed synthetic microphysical neural networks, called circuitoids, using precise combinations of spinal neuron subtypes derived from mouse stem cells. Circuitoids of purified excitatory interneurons were sufficient to generate oscillatory bursts with properties similar to in vivo central pattern generators. [eLife] Full Article | Press Release | Video The authors found that acute amyloid-β (Aβ) increases the expression of PIAS1 and Mcl-1 via activation of MAPK/ERK, and Aβ induction of PIAS1 enhances HDAC1 SUMOylation in rat hippocampus. [Cell Death Differ] Full Article The Survival of Motor Neuron Protein Acts as a Molecular Chaperone for mRNP Assembly Researchers employed a combination of biochemical and advanced imaging methods to demonstrate that survival of motor neuron promotes the molecular interaction between IMP1 protein and the 3′ UTR zipcode region of β-actin mRNA, leading to assembly of messenger ribonucleoprotein (mRNP) complexes that associate with the cytoskeleton to facilitate trafficking. [Cell Rep] Full Article | Press Release | Graphical Abstract The authors tested the efficacy of two human CNS neural stem cells lines in cervical spinal cord injury: one spinal cord injury (SCI), and one clinical cell lot/line (CCL) intended for use in the Pathway Study of cervical SCI in man. They assessed locomotor recovery and sensory function, as well as engraftment, migration, and fate. No evidence of efficacy of the CCL was observed; some data suggested a negative impact of the CCL on outcomes. [Stem Cell Reports] Full Article | Graphical Abstract While several studies showed that forebrain demyelination reactivates the subventricular zone (SVZ) triggering proliferation, ectopic migration, and oligodendrogenesis for myelin repair, the potential role of ciliated cells in this process was not investigated. Using conventional and lateral wall whole mount preparation immunohistochemistry in addition to electron microscopy in a forebrain-targeted model of experimental autoimmune encephalomyelitis (tEAE), resaerchers showed an early decrease in numbers of pinwheels, B1 cells, and E2 cells. [Glia] Abstract Investigators generated oligodendrocyte progenitor cells and mature oligodendrocytes within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. [PLoS One] Full Article | |
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REVIEWSPotential of GPCRs to Modulate MAPK and mTOR Pathways in Alzheimer’s Disease The authors discuss how Alzheimer’s disease may be addressed from two different points of view, neuroprotection or cognitive enhancement. Based on recent data, the mammalian target of rapamycin (mTOR) pathway arises as a versatile player whose modulation may impact on mechanisms of both neuroprotection and cognition. [Prog Neurobiol] Abstract Visit our reviews page to see a complete list of reviews in the neural cell research field. | |
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INDUSTRY NEWSAcorda Announces Positive Phase III Clinical Trial Results for CVT-301 Acorda Therapeutics, Inc. announced Phase III clinical data of CVT-301, showing a statistically significant improvement in motor function in people with Parkinson’s disease experiencing OFF periods. CVT-301 is an investigational, inhalable formulation of levodopa. It is being studied as a treatment for OFF periods in people with Parkinson’s disease taking an oral carbidopa/levodopa regimen. OFF periods refer to the re-emergence of Parkinson’s symptoms. [Acorda Therapeutics, Inc.] Press Release Merck announced that it will be stopping protocol 017, also known as the EPOCH study, a Phase II/III study evaluating verubecestat, an investigational small molecule inhibitor of the beta-site amyloid precursor protein cleaving enzyme 1, in people with mild-to-moderate Alzheimer’s disease. [Merck] Press Release Sanofi Initiates Phase II Clinical Trial to Evaluate Therapy for Genetic Form of Parkinson’s Disease Sanofi Genzyme announced the start of a Phase II trial of an investigational oral therapy for patients with Parkinson’s disease who carry a single copy of a gene mutation that is the most common genetic risk factor for the disease. The trial will assess the drug’s dynamics, efficacy and safety. This is the first industry-sponsored Phase II clinical trial in a genetically defined population of Parkinson’s disease. [Sanofi Genzyme] Press Release Neuraltus Pharmaceuticals Provides Enrollment Update on Confirmatory Phase II Study of NP001 in ALS Neuraltus Pharmaceuticals announced the confirmatory Phase II study of the company’s lead investigational treatment NP001 for amyotrophic lateral sclerosis (ALS) has enrolled 50 of the study’s 120 participants. [Neuraltus Pharmaceuticals] Press Release ​​​​​​​​​​​​Longevity Biotech, Inc. and the University of Nebraska Medical Center announced support from The Michael J. Fox Foundation for Parkinson’s Research (MJFF) to develop a novel immune transformative medicine, LBT-3627 to protect against nerve cell damage. The grant follows prior significant successes made through funding by the MJFF’s Therapeutic Pipeline Program. The research is linked to the Foundation’s new initiative for targeting inflammation as a disease-modifying strategy in Parkinson’s disease. [Longevity Biotech, Inc.] Press Release | |
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POLICY NEWSBroad Institute Wins Bitter Battle over CRISPR Patents A panel of US Patent and Trademark Office judges have determined that a series of patents granted for CRISPR-Cas9 gene editing to the Broad Institute of MIT and Harvard will stand. [Nature News] Editorial Henrietta Lacks’s Family Wants Compensation for Her Cells The eldest son of Henrietta Lacks wants compensation from Johns Hopkins University and possibly others for the unauthorized use of her cells in research that led to decades of medical advances. The cells taken from the 31-year-old after she died of an aggressive form of cervical cancer in 1951 were the first to live outside the body in a glass tube. They were dubbed the HeLa cells and have become the most widely used human cells that exist in scientific research. [The Washington Post] Editorial US Science Advisers Outline Path to Genetically Modified Babies Modified human embryos should be allowed if researchers meet strict criteria, says long-awaited National Academies report. [Nature News] Editorial German Scientists Regain Access to Elsevier Journals A stand-off in which dozens of German universities declined to pay for access to journals from publishing giant Elsevier has been partially resolved. [Nature News] Editorial
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EVENTSNEW 19th International Neuroscience Winter Conference Visit our events page to see a complete list of events in the community.
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JOB OPPORTUNITIESNEW Assistant or Associate Professor – Neuroscience (Burke-Cornell Medical Research Institute) NEW Scientist – Retina and CNS Degenerative Disease (University Health Network) Assistant Professor – Neuroscience (Pennsylvania State University) Postdoctoral Researcher – Stem Cell Differentiation (University of Oklahoma) Research Associate – Parkinson’s Disease (University of Bristol) PhD Position(s) – Neurosciences/Neurobiology (EU-GliaPhD) Neuroscientist – Precision Neurotherapeutics (University of California Davis) Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College) Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.
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Home Neural Cell News Volume 11.06 | Feb 15 2017