Neural Cell News Volume 13.05 | Feb 13 2019

TOP STORY

Chimpanzee Brain Organoids Hint at Secrets of Human Evolution

In a new study, co-first author Aparna Bhaduri, PhD, a postdoctoral researcher in the Kriegstein lab, deconstructed human and chimpanzee organoids at different stages of development, allowing her to directly compare the specific cell types and genetic programs that orchestrate the growth of the chimp and human brain. [Press release from University of California San Francisco discussing online prepublication in Cell] Press Release | Abstract

(Ranked by impact factor of the journal)

Mitophagy Inhibits Amyloid-β and Tau Pathology and Reverses Cognitive Deficits in Models of Alzheimer’s Disease

Mitophagy diminished insoluble amyloid-β (Aβ) 1-42 and Aβ1-40 and prevented cognitive impairment in an APP/PS1 mouse model through microglial phagocytosis of extracellular Aβ plaques and suppression of neuroinflammation. Mitophagy enhancement abolished Alzheimer’s disease-related tau hyperphosphorylation in human neuronal cells and reversed memory impairment in transgenic tau nematodes and mice. [Nat Neurosci] Abstract

BMP-Dependent Synaptic Development Requires Abi-Abl-Rac Signaling of BMP Receptor Macropinocytosis

Investigators found that abelson interactor (Abi) acted downstream of Abl and Rac1, and that BMP ligand glass bottom boat induced macropinocytosis dependent on Rac1/SCAR signaling, Abl-mediated Abi phosphorylation, and BMP receptor activation. [Nat Commun] Full Article

Hyperoxygenation Revitalizes Alzheimer’s Disease Pathology through the Upregulation of Neurotrophic Factors

Hyperoxygenation treatment increased the expression of BDNF, NT3, and NT4/5 through the upregulation of MeCP2/p-CREB activity in HT22 cells in vitro and in the hippocampus of mice. [Aging Cell] Full Article

Chemical Conversion of Human Fetal Astrocytes into Neurons through Modulation of Multiple Signaling Pathways

Chemically converted human neurons survived >7 months in culture, fired repetitive action potentials, and displayed robust synaptic burst activities. Interestingly, cortical astrocyte-converted neurons were mostly glutamatergic, while midbrain astrocyte-converted neurons could yield some GABAergic neurons in addition to glutamatergic neurons. [Stem Cell Reports] Full Article | Press Release

Cellular α-Synuclein Pathology Is Associated with Bioenergetic Dysfunction in Parkinson’s iPSC-Derived Dopamine Neurons

Induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) from Parkinson’s disease patients carrying mutations showed increased intracellular α-synuclein (αSyn; SNCA) accumulation, and DAn from patients carrying the SNCA triplication displayed oligomeric αSyn pathology and elevated αSyn extracellular release. [Hum Mol Genet] Abstract | Full Article

Astrocytic miR-324-5p Is Essential for Synaptic Formation by Suppressing the Secretion of CCL5 from Astrocytes

The expression of chemokine ligand 5 (CCL5) was elevated in Dicer-deleted astrocytes which led to significant augmentation of secreted CCL5 in astrocyte-conditioned medium (ACM). In neurons treated with Dicer KO-ACM, CCL5 supplementation inhibited the MAPK/CREB signaling pathway and exacerbated synaptic formation deficiency, while CCL5 knockdown partially rescued the synapse degeneration. [Cell Death Dis] Full Article

A30P Mutant α-Synuclein Impairs Autophagic Flux by Inactivating JNK Signaling to Enhance ZKSCAN3 Activity in Midbrain Dopaminergic Neurons

The authors identified that A30P mutant α-synuclein resulted in reduced autophagy flux through promoting the decrease of autophagosomal membrane-associated protein LC3 and the increase of SQSTM1/p62 protein levels in midbrain dopaminergic neurons, due to the transcriptional repressor ZKSCAN3 trafficking from the cytoplasm to the nucleus. [Cell Death Dis] Full Article

Downregulation of PRMT1 Promotes the Senescence and Migration of a Non-MYCN Amplified Neuroblastoma SK-N-SH Cells

Stable protein arginine methyltransferase 1-knockdown (PRMT1-KD) cells showed reduced growth rates and cell cycle arrest at G2/M. They also exhibited senescent phenotypes and increased p53 expression. p21 and PAI-1, which are two p53 downstream targets critical for senescence, were significantly induced in SK-N-SH cells subjected to either PRMT1-KD or inhibitor treatment. [Sci Rep] Full Article

Automated Microfluidic Cell Culture of Stem Cell Derived Dopaminergic Neurons

Scientists constructed an automated cell culture platform optimized for long-term maintenance and monitoring of different cells in 3D microfluidic cell culture devices. Using this system, they continuously monitored the differentiation of Parkinson’s disease patient derived human neuroepithelial stem cells into midbrain specific dopaminergic neurons. [Sci Rep] Full Article

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Oxidative Stress, Dysfunctional Glucose Metabolism and Alzheimer’s Disease

The brain mostly uses glucose for energy, but in Alzheimer’s disease (AD) and amnestic mild cognitive impairment glucose metabolism is dramatically decreased, probably owing, at least in part, to oxidative damage to enzymes involved in glycolysis, the tricarboxylic acid cycle and ATP biosynthesis. The authors summarize current research on the interplay and sequence of these processes and suggest potential pharmacological interventions to retard AD progression. [Nat Rev Neurosci] Abstract

Dementia in Down Syndrome: Unique Insights for Alzheimer’s Disease Research

Investigators evaluate the similarities and differences between the pathological cascades and genetics underpinning Down syndrome and Alzheimer’s disease with the aim of providing a platform for common exploration of these disorders. [Nat Rev Neurol] Abstract

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Results on Efficacy of PMZ-1620, an Endothelin-B Agonist, from Ongoing Phase II Trial in Patients with Cerebral Ischemic Stroke Presented

Pharmazz, Inc. announced that data from the Phase II clinical study in patients with acute cerebral ischemic stroke were presented. [Press release from Pharmazz, Inc. (PR Newswire Association LLC.) discussing research presented at the International Stroke Conference 2019, Honolulu] Press Release

Poster Presented at International Stroke Conference Describing Diffusion’s On-Ambulance Phase II Trial with TSC for Treating Acute Stroke

Diffusion Pharmaceuticals Inc. announced the presentation of a poster detailing an innovative on-ambulance Phase II study with the company’s lead drug trans sodium crocetinate (TSC) for the treatment of acute stroke. [Press release from Diffusion Pharmaceuticals Inc. discussing research presented at the International Stroke Conference 2019, Honolulu] Press Release

NuvOx Pharma’s NVX-208 Shows Positive Results in Phase Ib/II Stroke Trial

The randomized Phase Ib/II trial tested acute ischemic stroke patients given placebo or low, medium, or high doses of NVX-208. The primary endpoint was safety, which was demonstrated at all three dose levels. [Press release from NuvOx Pharma (Business Wire, Inc.) discussing research presented at the International Stroke Conference 2019, Honolulu] Press Release

Medicenna Presents Promising Clinical Data from Phase IIb Recurrent Glioblastoma Trial of MDNA55

Medicenna Therapeutics Corp. reported interim data from its on-going Phase IIb trial of MDNA55 for the treatment of recurrent glioblastoma. [Press release from Medicenna Therapeutics Corp. discussing research presented at the 5^th Annual Immuno-Oncology 360 Conference, New York] Press Release

BioArctic’s Product Candidate SC0806 for Treatment of Patients with Complete Spinal Cord Injury Is Now in Phase II

BioArctic AB announced that the first patient in the second panel of the Phase I/II study now has been treated with SC0806. This means that the study with the product candidate SC0806 for complete spinal cord injury has progressed into Phase II. [BioArctic AB] Press Release

VBI Vaccines Announces Third Positive DSMB Review in Phase I/IIa Study of VBI-1901 in Recurrent GBM Patients

VBI Vaccines Inc. announced that the independent Data and Safety Monitoring Board (DSMB) completed its third and final safety assessment of Part A of the ongoing Phase I/IIa clinical study of VBI-1901 in recurrent glioblastoma (GBM) patients. [VBI Vaccines Inc.] Press Release

BioArctic: US Food and Drug Administration Approves Investigational New Drug Application for ABBV-0805

BioArctic AB announced today that AbbVie has received approval from the FDA of the Investigational New Drug application for ABBV-0805. ABBV-0805 is a result of a strategic research alliance between BioArctic and AbbVie focused on the development of a potential immunotherapy for Parkinson’s disease. [BioArctic AB] Press Release

Parkinson’s Disease: ProMIS Neurosciences Identifies Several Antibody Drug Candidates Showing Best-in-Class Selectivity for Toxic Forms of Alpha-Synuclein Compared to Other Therapeutic Antibodies in Development

ProMIS Neurosciences, Inc. announced the identification of several monoclonal antibody drug candidates that selectively target toxic forms of the protein alpha-synuclein, considered to be a root cause of Parkinson’s disease. [ProMIS Neurosciences, Inc.] Press Release

NeuroCycle Therapeutics Awarded NIH SBIR Grant to Study Next-Generation Treatment of Dravet Syndrome

NeuroCycle Therapeutics, Inc. announced that is has been awarded a $0.5M Small Business Innovation Research (SBIR) grant from the National institute of Neurological Disorders and Stroke to evaluate its advanced subtype-selective GABAA receptor modulators, NCT10004 and NCT10015, in models of Dravet Syndrome. [NeuroCycle Therapeutics, Inc.] Press Release

INmune Bio Awarded a $1 Million Grant for the Development of XPro1595 for the Treatment of Alzheimer’s Disease

INmune Bio, Inc. announced that it has been awarded a grant to receive $1,000,000 from the Alzheimer’s Association to advance XPro1595, a novel therapy targeting neuroinflammation as a cause of Alzheimer’s disease. [INmune Bio, Inc.] Press Release

FEBS | EMBO Women in Science Award 2019 Awarded to Sara Linse

Sara Linse receives the award for her contribution to the understanding of the molecular mechanisms of protein self-assembly in Alzheimer’s disease and related neurodegenerative disorders. In addition, the award recognizes her varied activities in support of science and society. [EMBO] Press Release

Restructure Spurs Protest at Indonesia’s Largest Research Institution

Hundreds of scientists in Indonesia protested against a major reorganization of the country’s largest research institution that is set to relocate more than 1,400 science-support jobs. The head of the Indonesian Institute of Sciences (LIPI), Laksana Tri Handoko, says the changes will make the organization more efficient and will allow scientists to concentrate on research, which will help to transform LIPI into a world-class research institute. [Nature News] Editorial

Ukraine’s Science Revolution Stumbles Five Years On

Ukraine’s science system is in a precarious state, despite promised improvements in the wake of a revolution five years ago that aligned the country with the European Union. [Nature News] Editorial

NEW 3^rd SUNRiSE Meeting : New Advances in Cancer Stem Cells
May 16-17, 2019
Nice, France

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

NEW Senior Scientist – Neuroscience (STEMCELL Technologies Inc.)

NEW Postdoctoral Scholarship – Glioblastoma Stem Cell Research (Lund University)

Postdoctoral Research Fellow – Brain Tumor Biology (University of Bergen)

Postdoctoral Position – Neurobiology (Karolinska Institutet)

Postdoctoral Position – Neurophysiology (University Medical Center Hamburg Eppendorf)

Post Doctoral Scholarship – Brain Tumor Biology (Lund University)

Postdoctoral Scholar – Brain Tumor Biology (Lund University)

Faculty Positions – Developmental Neurosciences (Kent State University)

Postdoctoral Scientist – Regenerative Plasticity of Neural Circuits (Cedars-Sinai Medical Center)

Postdoctoral Position – Stem Cells & Neurodegeneration (Lund University)

Assistant Member – Developmental Neurobiology (St. Jude Children’s Research Hospital)

Associate Professor/Assistant Professor – Neuroscience (Hong Kong Baptist University)

Postdoctoral Fellowship – Alzheimer’s & Cerebrovascular Disease (Schepens Eye Research Institute/Massachusetts Eye and Eaar)

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