Neural Cell News Volume 10.47 | Nov 30 2016

TOP STORY

Nigral Dopaminergic PAK4 Prevents Neurodegeneration in Rat Models of Parkinson’s Disease

The authors report that p21-activated kinase 4 (PAK4) is a key survival factor for dopaminergic (DA) neurons. They observed PAK4 immunoreactivity in rat and human DA neurons in brain tissue, but not in microglia or astrocytes. PAK4 activity was markedly decreased in postmortem brain tissue from Parkinson’s Disease (PD) patients and in rodent models of PD. Expression of constitutively active PAK4^S445N/S474E protected DA neurons in both the 6-hydroxydopamine and α-synuclein rat models of PD and preserved motor function. [Sci Transl Med] Abstract

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Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-Degenerative Factors

Investigators showed that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identified Dusp16 as a new axonal preserving factor. [Neuron] Abstract

Toll-Like Receptor 2 Is Increased in Neurons in Parkinson’s Disease Brain and May Contribute to Alpha-Synuclein Pathology

Scientists examined the expression of toll-like receptor (TLR2) in postmortem brain tissue from Parkinson’s disease (PD) patients and matched controls. They confirmed that TLR2 is increased in PD brain, and found that levels of TLR2 correlate with the accumulation of pathological α-synuclein. TLR2 was expressed on neurons as well as microglia; however, the neuronal rather than glial expression of TLR2 was significantly increased in PD brain in accordance with disease staging, and TLR2 was strongly localized to α-synuclein positive Lewy bodies. [Acta Neuropathol] Full Article | Press Release

Parvalbumin- and Vasoactive Intestinal Polypeptide-Expressing Neocortical Interneurons Impose Differential Inhibition on Martinotti Cells

Researchers showed by means of optogenetics that Martinotti cells (MC) in layers II/III of the mouse primary somatosensory cortex are inhibited by both parvalbumin (PV)- and vasoactive intestinal polypeptide (VIP)-expressing cells. Paired recordings revealed stronger synaptic input onto MC from PV cells than from VIP cells. Moreover, PV cell input showed frequency-independent depression, whereas VIP cell input facilitated at high frequencies. These differences in the properties of the two unitary connections enable disinhibition with distinct temporal features. [Nat Commun] Full Article

Transduction of Group I MGluR-Mediated Synaptic Plasticity by β-arrestin2 Signaling

Investigators tested whether group I mGluRs require β-arrestin signaling during specific forms of plasticity at hippocampal excitatory synapses. They found that genetic ablation of β-arrestin2, but not β-arrestin1, resulted in deficits in plasticity mediated by mGlu1 receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal neurons. [Nat Commun] Full Article

Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A

Epileptic encephalopathies are a catastrophic group of epilepsies characterized by refractory seizures and cognitive arrest, often resulting from abnormal brain development. Scientists have identified an epileptic encephalopathy additionally featuring cerebral calcifications and coarse facial features caused by recessive loss-of-function mutations in DENND5A. [Am J Hum Genet] Abstract | Press Release

Accelerated Cell Divisions Drive the Outgrowth of the Regenerating Spinal Cord in Axolotls

Researchers showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions. They refined the analysis of cell proliferation in space and time and identified a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time. Their model shows that while cell influx and neural stem cell activation play a minor role, the acceleration of the cell cycle is the major driver of regenerative spinal cord outgrowth in axolotls. [eLife] Full Article

Novel KDM1A Inhibitors Induce Differentiation and Apoptosis of Glioma Stem Cells via Unfolded Protein Response Pathway

Investigators determined whether KDM1A modulates glioma stem cells (GSCs) stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. [Oncogene] Abstract

Proteome and Secretome Characterization of Glioblastoma-Derived Neural Stem Cells

Researchers performed quantitative proteomics to globally characterize and compare total proteome plus the secreted proteome (secretome) between glioblastoma multiforme-derived neural stem (GNS) cells and neural stem cells. Their findings support the notion that increased cell-matrix and cell-cell adhesion molecules play a crucial role in promoting the tumor initiating and infiltrative properties of GNS cells. [Stem Cells] Abstract

Self-Healing Polysaccharide-Based Hydrogels as Injectable Carriers for Neural Stem Cells

Scientists developed a biocompatible self-healing polysaccharide-based hydrogel system as a novel injectable carrier for the delivery of neural stem cells. [Sci Rep] Full Article

Elimination of Proliferating Cells from CNS Grafts Using a Ki67 Promoter-Driven Thymidine Kinase

Pluripotent stem cell-based cell therapy is an attractive concept for neurodegenerative diseases, but can lead to tumor formation. The authors describe how a cell cycle promoter-driven suicide gene approach allows killing of proliferating undifferentiated precursor cells without expression of the suicide gene in mature neurons. [Mol Ther Methods Clin Dev] Full Article

Mechanisms Linking Circadian Clocks, Sleep, and Neurodegeneration

In this Review, the authors explore potential cellular and molecular mechanisms linking circadian dysfunction and sleep loss to neurodegenerative diseases, with a focus on Alzheimer’s disease. They examine the interplay between central and peripheral circadian rhythms, circadian clock gene function, and sleep in maintaining brain homeostasis, and discuss therapeutic implications. [Science] Abstract

Cerebral Cortical Neuron Diversity and Development at Single-Cell Resolution

The authors review early efforts, and discuss future challenges and opportunities, in applying single-cell RNA sequencing (scRNA-seq) to the elucidation of neuronal subtypes and their development. [Curr Opin Neurobiol] Abstract

Visit our reviews page to see a complete list of reviews in the neural cell research field.

£1.1m Boost for Research into Spinal Cord Repair

The European research team has received £1.1 million (€1.3m) to investigate how zebrafish are able to repair and replace damaged nerve cells. Researchers will explore how these mechanisms can be triggered in other animals and human cells. [University of Edinburgh] Press Release

International Consortium of Complement Experts Receives €1.3 Million Grant to Study Role of MASP-2 and Lectin Pathway in Traumatic Brain Injury

Omeros Corporation announced that an international consortium of complement experts from Italy, United Kingdom, Germany, Spain and Poland was awarded €1.3 million in grant funding to study the benefits of inhibiting mannan-binding lectin-associated serine protease-2 (MASP-2) and the lectin pathway in traumatic brain injury. Omeros’ OMS721 is a human monoclonal antibody that inhibits MASP-2, which is the effector enzyme of the lectin pathway of the complement system. Omeros controls the worldwide rights to MASP-2 and all therapeutics targeting MASP-2. [Omeros Corporation] Press Release

New Canadian Investments in ALS Research Reflect Growing Knowledge About the Disease and Increasing Likelihood of Effective Treatments Being Developed

The ALS Society of Canada, in partnership with Brain Canada, announced $4.5 million in funding for nine new ALS research projects. [The ALS Society of Canada] Press Release

DFG to Fund 14 New Collaborative Research Centres

The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) will establish 14 new Collaborative Research Centers (CRCs). They will establish research networks to investigate topics such as practices of comparison, neutrinos, dark matter, and the robustness of vision. The new CRCs will receive a total of 117.4 million euros in funding. [The Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)] Press Release

jCyte Completes Enrollment for Phase I/IIa Safety Trial

jCyte has completed enrollment in a Phase I/IIa trial to study the safety of its stem cell therapy candidate for retinitis pigmentosa (RP). The trial included 28 patients with advanced RP, eight of whom have completed the one-year study. [jCyte] Press Release

FAU and Neuro Pharmalogics Enter into Licensing Agreement

Florida Atlantic University has entered into a licensing agreement with Neuro Pharmalogics, Incorporated. The portfolio of patents focuses on the protein kinase G pathway, which plays a pivotal role in several neurological conditions by controlling cortical spreading depolarization. [Florida Atlantic University] Press Release

Nature Cell Co., Ltd. Receives U.S. FDA Approval for Phase I and II Alzheimer’s Clinical Trial

Nature Cell Co., Ltd. announced AstroStem’s approval for Phase I and Phase II clinical trials for treatment of Alzheimer’s disease by the U.S. Food and Drug Administration (FDA). AstroStem is a therapeutic agent for adult stem cells that collects about 10g of fat from the patient’s own abdominal subcutaneous tissue and separates only pure stem cells into a finished product, which is repeatedly administered intravenously to the patient. [Nature Cell Co., Ltd. (PR Newswire Association LLC.)] Press Release

New U.S. Research Policy Board Would Aim to Slash Regulatory Paperwork

Easing the regulatory burden on U.S. academic research certainly isn’t as sexy as curing cancer or understanding how the brain works. But creating an advisory body focused on eliminating government red tape—a tiny provision in a 996-page bill to accelerate medical research that could become law next month—is no less important to maintaining the health of the research community than is the infusion of billions of dollars, higher education lobbyists say. [ScienceInsider] Editorial

UK Moves Closer to Allowing ‘Three-Parent’ Babies

The United Kingdom may soon become the first country to explicitly permit the birth of children from embryos modified to contain three people’s DNA. At the same time, new research backs up concerns that such a treatment — which aims to erase diseases transmitted by the DNA found in cellular structures called mitochondria — may not always be 100% effective. [Nature News] Editorial

Trump’s Pick for US Health Secretary Has Pushed to Cut Science Spending

Republican congressman Tom Price of Georgia is US President-elect Donald Trump’s pick to head the US Department of Health and Human Services. If he is confirmed by the Senate, Price would oversee the National Institutes of Health, the Centers for Disease Control and Prevention and the Food and Drug Administration. [Nature News] Editorial

Tracking the Trump Transition, Agency by Agency

As US president-elect Donald Trump begins to sketch out the priorities of his administration, Nature tracks the key issues and likely leaders of vital science and research agencies. [Nature News] Editorial

NEW Primary and Secondary Brain Tumors
February 19-22, 2017
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NEW Post-Doctoral Research Fellow – Neurobiology (Institut of Molecular Biology (IMB))

NEW Assistant Professor – Molecular Therapeutics of Cancer (Dartmouth College)

Postdoctoral Fellow – Neurobiology of Hunger And Other Homestatic Drivers (Beth Israel Deaconess Medical Center/Harvard Medical School)

Neuroscience Postdoctoral Fellow (Harvard University)

Research Associate Position in Neural Rehabilitation Experiments (Nanyang Technological University)

Postdoctoral Researcher – Alzheimer’s Disease (University of Arkansas)

Computational Biologist – Aging Brain (Columbia University)

Postdoctoral Fellow – Parkinson’s Disease Research (Van Andel Research Institute)

NYSCF Investigator – Stem Cell And Neuroscience (New York Stem Cell Foundation)

Postdoctoral Fellow – Neural Stem/Progenitor Cells (University of California – San Francisco)

Postdoctoral Fellow – Genetic and Epigenetic Features Parkinson’s and Alzheimer’s Diseases (Van Andel Research Institute)

PhD – Neural Circuits (The International Max Planck Research School for Neural Circuits)

Assistant Professor (Tenure) – Developmental Biology)

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