Neural Cell News Volume 12.27 | Jul 11 2018

TOP STORY

Graphene Quantum Dots Prevent α-Synucleinopathy in Parkinson’s Disease

Scientists showed that graphene quantum dots (GQDs) inhibited fibrillization of α-synuclein (α-syn) and interacted directly with mature fibrils, triggering their disaggregation. GQDs could rescue neuronal death and synaptic loss, reduce Lewy body and Lewy neurite formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of α-syn pathology provoked by α-syn preformed fibrils. [Nat Nanotechnol] Abstract | Press Release

(Ranked by impact factor of the journal)

Th17 Lymphocytes Induce Neuronal Cell Death in a Human iPSC-Based Model of Parkinson’s Disease

After co-culture with T lymphocytes or the addition of IL-17, Parkinson’s disease induced pluripotent stem cell-derived midbrain neurons underwent increased neuronal death driven by upregulation of the IL-17 receptor (IL-17R) and NFκB activation. Blockage of IL-17 or IL-17R, or the addition of the FDA-approved anti-IL-17 antibody, secukinumab, rescued neuronal death. [Cell Stem Cell] Abstract | Press Release | Graphical Abstract

BCL3 Expression Promotes Resistance to Alkylating Chemotherapy in Gliomas

B cell CLL/lymphoma 3 (BCL-3) promoted a more malignant phenotype by inducing an epithelial-to-mesenchymal transition in glioblastomas through promoter-specific NF-κB dimer exchange. Carbonic anhydrase II was identified as a downstream factor promoting BCL-3–mediated resistance to chemotherapy. [Sci Transl Med] Full Article | Press Release

Activity-Dependent Degradation of the Nascentome by the Neuronal Membrane Proteasome

Researchers found that the neuronal-specific 20S membrane proteasome complex (NMP) degraded exclusively a large fraction of ribosome-associated nascent polypeptides that are being newly synthesized during neuronal stimulation. They identified the nascent protein substrates of the NMP, which included products encoding immediate-early genes, such as c-Fos and Npas4. [Mol Cell] Abstract | Press Release | Graphical Abstract

PICK1 Inhibits the E3 Ubiquitin Ligase Activity of Parkin and Reduces Its Neuronal Protective Effect

Investigators report that the Bin/Amphiphysin/Rvs domain of protein interacting with PRKCA1 (PICK1) bound to the really interesting new gene 1 domain of Parkin and potently inhibited the E3 ligase activity of Parkin by disrupting its interaction with UbcH7. Parkin translocated to damaged mitochondria and led to their degradation in neurons, whereas PICK1 robustly inhibited this process. [Proc Natl Acad Sci USA] Full Article

Cholinergic Homeostatic Synaptic Plasticity Drives the Progression of Aβ-Induced Changes in Neural Activity

Scientists presented evidence that early enhancement in synaptic activity was mediated by the Drosophila α7 nicotinic acetylcholine receptor and that, later, beta-amyloid (Aβ) peptide 42-induced inhibition of synaptic events was a consequence of Dα7-dependent homeostatic synaptic plasticity mechanisms induced by earlier hyperactivity. [Cell Rep] Full Article | Graphical Abstract

Aberrant Calcium Signaling in Astrocytes Inhibits Neuronal Excitability in a Human Down Syndrome Stem Cell Model

Compared with control isogenic astroglia, down syndrome astroglia exhibited more-frequent spontaneous calcium fluctuations, which reduced the excitability of co-cultured neurons. Suppressed neuronal activity could be rescued by abolishing astrocytic spontaneous calcium activity either chemically by blocking adenosine-mediated signaling or genetically by knockdown of inositol triphosphate receptors or S100B, a calcium binding protein coded on human chromosome 21. [Cell Rep] Full Article | Graphical Abstract

Distinct Molecular Signatures of Quiescent and Activated Adult Neural Stem Cells Reveal Specific Interactions with Their Microenvironment

Investigators showed that LeX^bright cells sorted from the adult mouse subventricular zone exhibited all the characteristic features of quiescent neural stem cells. They constituted a subpopulation of slowly dividing cells that were able to enter the cell cycle to regenerate the irradiated niche. [Stem Cell Reports] Full Article

GMP Production and Scale-Up of Adherent Neural Stem Cells with a Quantum Cell Expansion System

Researchers developed an expansion method using the hollow fiber quantum cell expansion (QCE) system. These QCE neural stem cells showed genetic and functional stability equivalent to those expanded by conventional flask-based methods. [Mol Ther Methods Clin Dev] Full Article

A Novel Small-Molecule Activator of Sirtuin-1 Induces Autophagic Cell Death/Mitophagy as a Potential Therapeutic Strategy in Glioblastoma

The authors demonstrated that compound F0911-7667 (Comp 5)-induced autophagic cell death via the AMPK-mTOR-ULK complex in U87MG and T98G cells. Comp 5-induced mitophagy by the sirtuin-1 (SIRT1)–PINK1–Parkin pathway. They revealed that Comp 5 could induce autophagy/mitophagy by downregulating 14-3-3γ, catalase, profilin-1, and HSP90α. [Cell Death Dis] Full Article

Coordinated Autophagy Modulation Overcomes Glioblastoma Chemoresistance through Disruption of Mitochondrial Bioenergetics

Investigators showed that coordinated upregulation of autophagy followed by its inhibition prior to chemotherapy decreased electron transfer system and oxidative phosphorylation capacity, impaired mitochondrial fission and fusion dynamics and enhanced apoptotic cell death onset in terms of cleaved caspase 3 and cleaved PARP expression. [Sci Rep] Full Article

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Multidimensional Communication in the Microenvirons of Glioblastoma

An important component of glioblastoma growth is communication with and manipulation of other cells in the brain environs, which supports tumor progression and resistance to therapy. Understanding these multidimensional communications between the tumor and the cells in its environs could open new avenues for therapy. [Nat Rev Neurol] Abstract

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PBT434 Data to Be Presented at the International Congress of Parkinson’s Disease and Movement Disorders

Prana Biotechnology Ltd announced it will be presenting further pre-clinical evidence for PBT434. The data to be presented will include new in-vivo evidence of the efficacy of PBT434 to prevent neuron loss and improve function in an animal model of Multiple system atrophy, an important cause of atypical Parkinsonism. [Press release from Prana Biotechnology Limited discussing research to be presented at the International Congress of Parkinson’s Disease and Movement Disorders, Hong Kong] Press Release

Orion Has Started a Phase III Trial to Develop a Drug for ALS – the Patient Recruitment Has Begun

Orion has recruited the first patients in the Phase III clinical trial in which orally administered levosimendan is being evaluated for the treatment of symptoms of ALS. The purpose of the trial is to demonstrate that orally administered levosimendan, by enhancing respiratory muscle function, can help maintain breathing capacity and so benefit overall functioning of patients with ALS. [Orion Corporation] Press Release

Eisai and Biogen Announce Positive Topline Results of the Final Analysis for BAN2401 at 18 Months

Eisai Co., Ltd. and Biogen Inc. announced positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer’s disease. The study achieved statistical significance on key predefined endpoints evaluating efficacy at 18 months on slowing progression in Alzheimer’s Disease Composite Score and on reduction of amyloid accumulated in the brain as measured using amyloid-positron emission tomography. [Biogen] Press Release

UHN Launches Krembil Brain Institute

On June 20, UHN established the Krembil Brain Institute (link is external) to formally create an academic health sciences entity that harmonizes the clinical and research priorities in the neurosciences. This new institute will help clinicians, scientists and researchers based at Toronto Western Hospital and across UHN work together to seek better treatments and cures for diseases of the brain, spine and nerves. [University Health Network] Press Release

Neuroscientist Dr. Li Gan to Lead Appel Alzheimer’s Research Institute

Dr. Li Gan, a neuroscientist internationally acclaimed for her research into neurodegenerative diseases, has been appointed director of the Helen and Robert Appel Alzheimer’s Disease Research Institute at Weill Cornell Medicine, effective July 1. [Weill Cornell Medicine] Press Release

Chinese Researchers to Get More Autonomy Over Lab Spending

Chinese Premier Li Keqiang says the country will ease restrictive rules governing how research funds are used, and cut red tape for researchers. Revised rules are designed to help researchers focus on their work and compete with their counterparts globally. [Nature News] Editorial

UK Universities Fall Short on Reporting Misconduct Investigations

The United Kingdom should establish a committee to monitor efforts by the nation’s universities to properly conduct misconduct investigations, a parliamentary inquiry recommends. The guidance follows a new report released, revealing that one in four UK universities does not comply with research integrity guidelines released six years ago. [Nature News] Editorial

NEW Gordon Research Conferences: Notch Signaling in Development, Regeneration and Disease
July 22-27, 2018
Lewiston, Maine, United States

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

NEW Senior/Principal Fellow or Professor – Program Leader for Animal Models (UK Dementia Research Institute)

Scientist/Assistant Professor – Neuroscience (The Hospital for Sick Children)

Postdoctoral Associate – Cerebral Organoids (Weill Cornell Medicine)

Postdoctoral Position – Spinal Cord Development (The Francis Crick Institute)

Postdoctoral Positions – Neurodevelopmental Disorders (University of Copenhagen)

Postdoctoral Research Scientist – Psychiatric Disorders (Columbia University)

Project Leader/Director – Neurodegenerative Research (Servier Group)

Postdoctoral Fellows – Neuroscience (Louisiana State University)

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

Postdoctoral Associate – hiPSC-Based Brain Organoids (Rutgers University)

Multiple Faculty Positions – Neuroscience and Neuroengineering (Tsinghua University)

Faculty Members – Neuroscience (Mercer University)

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