Neural Cell News Volume 12.34 | Aug 29 2018

TOP STORY

Reciprocal Control of Excitatory Synapse Numbers by Wnt and Wnt Inhibitor PRR7 Secreted on Exosomes

Exosomal proline-rich 7 (PRR7) was uptaken by neurons through membrane fusion and eliminated excitatory synapses in neighboring neurons. PRR7 knockdown in sparse neurons greatly increased excitatory synapse numbers in all surrounding neurons. These non-cell autonomous effects of PRR7 were effectively negated by augmentation or blockade of Wnt signaling. [Nat Commun] Full Article

(Ranked by impact factor of the journal)

Human iPSC-Derived Trigeminal Neurons Lack Constitutive TLR3-Dependent Immunity That Protects Cortical Neurons from HSV-1 Infection

The resulting trigeminal ganglion (TG) neurons were of sensory identity and exhibited robust responses to heat, cold, and inflammatory pain. Unlike control cortical neurons, both control and toll-like receptor 3 (TLR3)-deficient TG neurons were highly susceptible to herpes simplex virus type 1 (HSV-1). [Proc Natl Acad Sci USA] Abstract

Early Postnatal Behavioral, Cellular, and Molecular Changes in Models of Huntington Disease Are Reversible by HDAC Inhibition

Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking were accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. [Proc Natl Acad Sci USA] Full Article

Pathological Missorting of Endogenous MAPT/Tau in Neurons Caused by Failure of Protein Degradation Systems

Blocking protein degradation pathways with proteasomal or autophagy inhibitors dramatically increased the missorting of MAPT in dendrites on the neuritic side, suggesting that degradation of MAPT in dendrites is a major determinant for the physiological axonal distribution of MAPT. [Autophagy] Abstract

TLR5 Decoy Receptor as a Novel Anti-Amyloid Therapeutic for Alzheimer’s Disease

TLR5 ectodomain fused to human IgG4 Fc (TLR5Fc) bound to oligomeric and fibrillar amyloid β (Aβ) with high affinity, formed complexes with Aβ, and blocked Aβ toxicity. Oligomeric and fibrillar Aβ modulated flagellin-mediated activation of human TLR5 but did not, by itself, activate TLR5 signaling. [Autophagy] Full Article | Press Release | Graphical Abstract

Human Induced Pluripotent Stem Cell-Derived Microglia-Like Cells Harboring TREM2 Missense Mutations Show Specific Deficits in Phagocytosis

Induced pluripotent stem cell-derived microglia-like cells expressed microglial markers and secreted higher levels of TREM2 than primary macrophages. TREM2 expression and secretion were reduced in variant lines. TREM2 missense mutations caused a marked impairment in the phagocytosis of apoptotic bodies, but not in Escherichia coli or zymosan substrates. [Cell Rep] Full Article | Graphical Abstract

The Matricellular Protein R-Spondin 2 Promotes Midbrain Dopaminergic Neurogenesis and Differentiation

Only roof plate-specific spondin 2 (RSPO2) and floor plate-specific, spondin 1 (SPON1) were expressed at high levels during midbrain dopaminergic (mDA) neurogenesis, and the receptor LGR5 was expressed by midbrain floor plate progenitors. RSPO2, but not SPON1, specifically promoted the differentiation of mDA neuroblasts into mDA neurons in mouse primary cultures and embryonic stem cells. [Stem Cell Reports] Full Article | Graphical Abstract

Chemical Screening Identifies Enhancers of Mutant Oligodendrocyte Survival and Unmasks a Distinct Pathological Phase in Pelizaeus-Merzbacher Disease

The authors defined an early pathological window characterized by endoplasmic reticulum (ER) stress and cell death as oligodendrocyte progenitor cells exited their progenitor state. They identified a compound, Ro 25-6981, which modulated the ER stress response and rescued mutant oligodendrocyte survival in jimpy, in vitro and in vivo, and in human Pelizaeus-Merzbacher disease oligocortical spheroids. [Stem Cell Reports] Full Article

Downregulation of SNCA Expression by Targeted Editing of DNA-Methylation: A Potential Strategy for Precision Therapy in PD

Scientists developed a system, comprised of an all-in-one lentiviral vector, for targeted DNA-methylation editing within intron 1. Applying the system to human induced pluripotent stem cell-derived dopaminergic neurons from a Parkinson’s disease (PD)-patient with the SNCA-triplication, resulted in fine downregulation of SNCA-mRNA and protein mediated by targeted DNA-methylation at intron 1. [Mol Ther] Abstract | Graphical Abstract

Alpha-6 Integrin Promotes Radioresistance of Glioblastoma by Modulating DNA Damage Response and the Transcription Factor Zeb1

In cells downregulated for α6-integrin expression, researchers observed a decrease in cell survival after irradiation and an increase in radio-induced cell death. They demonstrated that inhibition of α6-integrin expression affected DNA damage checkpoint and repair. [Cell Death Dis] Full Article

Specific Inhibition of ADAM17/TACE Promotes Neurogenesis in the Injured Motor Cortex

Specific inhibition of ADAM17 activity by ADAM17-Pro overexpression increased the generation of new neurons in vitro. Local overexpression of ADAM17-Pro in injured cortex in vivo, mediated by lentiviral vectors, dramatically increased the number of neuroblasts observed at the lesion 14 days after injury. [Cell Death Dis] Full Article

Direct Generation of Human Cortical Organoids from Primary Cells

Cellular reprogramming and further differentiation techniques are costly and time-consuming and therefore, studies using this approach are often limited to a small number of samples. Scientists described a rapid and cost-effective method to reprogram somatic cells and the direct generation of cortical organoids in a 96-well format. [Stem Cells Dev] Abstract

Subscribe to one of our other 19 science newsletters such as Cancer Stem Cell News & ESC & iPSC News.

Interplay between Innate Immunity and Alzheimer Disease: APOE and TREM2 in the Spotlight

Investigators review the rapidly growing literature on the role of disease-associated microglia, TREM2 and APOE in the pathogenesis of Alzheimer disease and present an integrated view of innate immune function in Alzheimer disease. [Nat Rev Immunol] Abstract

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

Xenon Announces Positive XEN1101 Pharmacodynamic Data from Phase Ib TMS Study

Xenon Pharmaceuticals Inc. announced positive data from its XEN1101 Phase Ib transcranial magnetic stimulation (TMS) study. XEN1101 is a Kv7 potassium channel opener being developed by Xenon for the treatment of epilepsy. [Press release from Xenon Pharmaceuticals Inc. discussing research to be presented at the 13^th European Congress on Epileptology, Vienna] Press Release

KinoPharma and National Institutes for Quantum and Radiological Science and Technology Launch Collaborative Research Project for Exploring New Drug Development for Alzheimer’s Disease

KinoPharma, Inc., and the National Institutes for Quantum and Radiological Science and Technology announce that they have entered a contract for collaborative research on efficacy evaluation of the compound KPO1143, developed by KinoPharma, to prevent the accumulation of protein called tau, which is considered a cause of Alzheimer’s disease. [KinoPharma, Inc. (PR Newswire Association LLC.)] Press Release

Medicortex Finland Oy: Clinical Trial Extended for Detection of Mild Traumatic Brain Injury

Medicortex Finland announced that the Ethics Committee approved an additional site in the second clinical trial of ProbTBI^™, a diagnostic kit for mild Traumatic Brain Injury detection. Accelerated recruitment of patients will be performed in the central hospitals of Turku, Pori and Vaasa in Finland during the next few months. [Medicortex Finland (Business Wire, Inc.)] Press Release

Magnolia Neurosciences Corporation Announces That Its Subsidiary Receives $20 Million CPRIT Grant to Develop Novel Therapies to Treat Chemotherapy-Induced Neurological Conditions

Magnolia Neurosciences Corporation announced that Korysso Therapeutics, Inc. has been awarded a $19.95 million grant from the Cancer Prevention and Research Institute of Texas (CPRIT) to fund the development of a novel targeted therapy for the treatment of neurological conditions caused by chemotherapy. [Magnolia NeuroSciences] Press Release

Hesperos to Create Multi-Organ Human-on-a-Chip Model to Test Alzheimer’s Drugs

Hesperos, Inc., announced the receipt of a NIH Phase I Small Business Innovation Research grant from the National Institutes of Health National Institute on Aging to help create a new multi-organ “human-on-a-chip” model that can realistically mimic the biology of Alzheimer’s Disease and the effects of potential new therapies under realistic human physiological conditions. [Hesperos, Inc. (Business Wire, Inc.)] Press Release

Baylor Awarded CPRIT Grants for Research, Recruitment

Baylor College of Medicine has been awarded more than $31 million by the Cancer Prevention & Research Institute of Texas (CPRIT) to support new research, core facilities and recruitment of new faculty to support the fight against cancer. [Baylor College of Medicine] Press Release

NIH Investigating Whether U.S. Scientists Are Sharing Ideas with Foreign Governments

Fears that foreign governments are tapping U.S.-funded research for valuable information have reached the nation’s largest research funder, the National Institutes of Health (NIH) in Bethesda, Maryland. It sent a letter to more than 10,000 research institutions, urging them to ensure that NIH grantees are properly reporting their foreign ties. [ScienceInsider] Editorial

Publish Peer Reviews

Long shrouded in secrecy, the contents of peer review are coming into the open. In the past decade, outlets such as eLife, F1000Research, Royal Society Open Science, Annals of Anatomy, Nature Communications, PeerJ and EMBO Press have begun to publish referee reports. [Nature] Editorial

NEW EMBO-EMBL Symposia: Organoids: Modeling Organ Development and Disease in 3D Culture
September 10-13, 2018
Heidelberg, Germany

Visit our events page to see a complete list of events in the community.

NEW Postdoctoral Research Associate – Cell Biology of Neural Development (St Jude Children’s Research Hospital)

NEW Assistant Professor – Systems Neuroscience (Carnegie Mellon University)

Tenure Eligible Investigator – Neurobiology (Universite Bourgogne Franche-Comté)

Postdoctoral Position – Stem Cell-Based Modeling of Psychiatric Disease (Universitat Bonn)

Postdoctoral Position – Bioinformatic Analysis of Neural Development in Nematostella (University of Bergen)

Excellence in Science PhD Scholarship Award – Neuroscience (University of Technology Sydney)

Postdoctoral Research Scientist/Fellow – Neural Development and Neurodegenerative Diseases (Columbia University)

Postdoctoral Position – Molecular Mechanisms & Neural Circuits of Memory & Behavior (Rutgers University)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

Recruit Top Talent: Reach potential candidates by posting your organization’s career opportunities on the Connexon Creative Job Board at no cost.

Have we missed an important article or publication in Neural Cell News? Click here to submit!

Comments or suggestions? Submit your feedback here.