Neural Cell News Volume 12.19 | May 16 2018

TOP STORY

Diverse Parkinson’s-Related Disorders May Stem from Different Strains of Same Disease Protein

Different Parkinson’s-related brain disorders, called synucleionpathies, are characterized by misfolded proteins embedded in cells. Researchers found that the type of brain cell afflicted dictates which pathological form of α-synuclein protein becomes the disease culprit. [Press release from the Perelman School of Medicine discussing online prepublication in Nature] Press Release | Abstract

(Ranked by impact factor of the journal)

Expression of the DNA-Binding Factor TOX Promotes the Encephalitogenic Potential of Microbe-Induced Autoreactive CD8⁺ T Cells

In a model of central nervous system inflammation, scientists found that infection with lymphocytic choriomeningitis virus (LCMV), but not Listeria monocytogenes (Lm), drove autoimmunity. The DNA-binding factor TOX was induced in cytotoxic T lymphocytes during LCMV infection and was essential for their encephalitogenic properties, and its expression was inhibited by interleukin-12 during Lm infection. [Immunity] Abstract | Editorial

Targeted Inhibition of Histone H3K27 Demethylation Is Effective in High-Risk Neuroblastoma

Investigators performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome, and histone demethylase Jumonji D3. [Sci Transl Med] Full Article

RNP-Granule Assembly via Ataxin-2 Disordered Domains Is Required for Long-Term Memory and Neurodegeneration

The authors demonstrated that ataxin-2 intrinsically disordered regions, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo. [Neuron] Abstract

PCGF5 Is Required for Neural Differentiation of Embryonic Stem Cells

Scientists report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. [Nat Commun] Full Article

Targetable BET Proteins- and E2F1-Dependent Transcriptional Program Maintains the Malignancy of Glioblastoma

With mechanistic exploration of a next-generation chemical degrader of BET proteins, researchers revealed a profound and consistent impact of BET proteins on E2F1- dependent transcriptional program in both differentiated glioblastoma cells and brain tumor-initiating cells. [Proc Natl Acad Sci USA] Full Article

Estrogen Receptor β Controls Proliferation of Enteric Glia and Differentiation of Neurons in the Myenteric Plexus after Damage

Since the estrogen receptor β (ERβ) is expressed in enteric glial cells and neurons, the authors investigated whether a selective ERβ agonist, LY3201, can influence neuronal and glial cell differentiation. [Proc Natl Acad Sci USA] Abstract

Extracellular Forms of Aβ and Tau from iPSC Models of Alzheimer’s Disease Disrupt Synaptic Plasticity

To identify extracellular molecules that impair synaptic plasticity in the brain, researchers studied the secretomes of human iPSC-derived neuronal models of Alzheimer’s disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibited hippocampal long-term potentiation. [Cell Rep] Full Article | Graphical Abstract

SIRT1 Activation with Neuroheal Is Neuroprotective but SIRT2 Inhibition with AK7 Is Detrimental for Disconnected Motoneurons

Scientists compared the neuroprotective potentials of Sirtuin (SIRT)1 activation and SIRT2 inhibition in a mouse model of hypoglossal nerve axotomy. Both SIRT1 activation with NeuroHeal and SIRT2 inhibition with AK7 protected NSC-34 motor neuron-like cells against endoplasmic reticulum stress in vitro. [Cell Death Dis] Full Article

Neuron-Specific HuR-Deficient Mice Spontaneously Develop Motor Neuron Disease

To study the neuron-specific function of HuR, investigators generated inducible, neuron-specific HuR-deficient mice of both sexes. After tamoxifen-induced deletion of HuR, these mice developed a phenotype consisting of poor balance, decreased movement, and decreased strength. [J Immunol] Abstract

Physiological Aβ Concentrations Produce a More Biomimetic Representation of the Alzheimer’s Disease Phenotype in iPSC Derived Human Neurons

Scientists investigated chronic, pathologically-relevant amyloid-β (Aβ) oligomer concentrations to induce an electrophysiological phenotype that is more representative of early Alzheimer’s disease progression compared to an acute high-dose application in human cortical neurons. [ACS Chem Neurosci] Abstract

Effect of Bmi1 Over-Expression on Gene Expression in Adult and Embryonic Murine Neural Stem Cells

Genes whose expression was altered by perturbations in Bmi1 levels in neural stem cells were mostly distinct from those affected in other multipotent stem/progenitor cells, such as those from liver and lung, aside from a small core of common targets that was enriched for genes associated with cell migration and mobility. [Sci Rep] Full Article

Dissecting Spinal Cord Regeneration

The inability to recover functions lost after severe spinal cord injury has been recognized for millennia and was first attributed to a failure of spinal cord neural regeneration over 100 years ago. The last forty years have seen intense research into achieving such regeneration, but in spite of conceptual advances and many reports announcing successful interventions, progress has been slow and often controversial. [Nature] Abstract

New Approaches for Brain Repair—from Rescue to Reprogramming

New approaches using stem-cell-derived cell products and direct cell reprogramming have opened up the possibility of reconstructing neural circuits and achieving better repair. The authors summarize the history of neural repair and then discuss these new therapeutic approaches, especially with respect to chronic neurodegenerative disorders. [Nature] Abstract

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Canadian Researchers Find Key Players for Building and Repairing the Brain

Research by Dr. Freda Miller and her team at the Hospital for Sick Children and the University of Toronto has determined how brain stem cells and the environment they live within collaborate to build brain circuits during development, discoveries that have led to a better understanding of neurodevelopmental disorders in children. [Press release from Canadian Association for Neuroscience (EurekAlert!) discussing research presented at the 2018 Canadian Neuroscience Meeting, Vancouver] Press Release

Marcus Center for Cellular Cures at Duke to Tackle Autism, MS, Stroke

The Marcus Center for Cellular Cures at Duke University School of Medicine has been established to bring together physicians and faculty across medicine and engineering at Duke to develop cellular and biological therapies for autism, cerebral palsy, stroke, and related brain disorders. [Duke University School of Medicine] Press Release

Ziopharm Hits Pause on Planned Pivotal Brain Cancer Trial

Ziopharm Oncology has hit pause on a planned pivotal trial of Ad-RTS-hIL-12 in brain cancer patients. Management took the action after technical issues slowed progress of the inducible adenoviral vector. [Ziopharm Oncology (FierceBiotech)] Press Release

Novartis Announces FDA Approval of Gilenya^® as the First Disease-Modifying Therapy for Pediatric Relapsing Multiple Sclerosis

Novartis announced that the FDA has approved Gilenya^® for the treatment of children and adolescents 10 to less than 18 years of age with relapsing forms of MS, making it the first disease-modifying therapy indicated for these patients. [Novartis] Press Release

Huge Gender Disparity in Cancer Research Funding in U.K.

The analysis examined data on both public and philanthropic grants given to support cancer research in the U.K. Male PIs were awarded 69 percent of the grants, and their grants were on average 1.3 times as large as those given to women, so that they received 78 percent of the total money allocated. [The Scientist] Editorial

Patient Registries to Bolster Cell- and Gene-Therapy Clinical Trial Data

As the first personalized cell and gene therapies are approved from small clinical trials, researchers propose the creation of publicly accessible databases to pull together real-world results. [The Scientist] Editorial

Sacked Japanese Biologist Gets Chance to Retrain at Crick Institute

Prominent cell biologist Yoshinori Watanabe, who was dismissed by the University of Tokyo last month, is attempting to put his past behind him by embarking on an intensive retraining program with Nobel prizewinner Paul Nurse in London. The university dismissed Watanabe after an investigation concluded that he had committed scientific misconduct. [Nature News] Editorial

FDA Seeks Permanent Injunctions against Two Stem Cell Clinics

The FDA, in two complaints filed in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements. [U.S. Food and Drug Administration] Press Release

NEW Gordon Research Conferences: Lysosomes and Endocytosis
June 17-22, 2018
Andover, New Hampshire, United States

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NEW Research Associate/Postdoctoral Position – Neurodegenerative Diseases (TU Dresden)

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