Neural Cell News Volume 12.49 | Dec 12 2018

TOP STORY

Methotrexate Chemotherapy Induces Persistent Tri-Glial Dysregulation that Underlies Chemotherapy-Related Cognitive Impairment

The authors demonstrated persistent depletion of oligodendrocyte lineage cells in humans who received chemotherapy. Developing a mouse model of methotrexate chemotherapy-induced neurological dysfunction, they found a similar depletion of white matter OPCs, increased but incomplete OPC differentiation, and a persistent deficit in myelination. [Cell] Abstract | Press Release | Editorial | Graphical Abstract

(Ranked by impact factor of the journal)

WDR81 Regulates Adult Hippocampal Neurogenesis through Endosomal SARA-TGFβ Signaling

Researchers showed that ablation of WDR81 in adult neural progenitor cells markedly reduced adult hippocampal neurogenesis and impaired hippocampus-dependent learning. [Mol Psychiatry] Full Article

New Neurons Use Slit-Robo Signaling to Migrate through the Glial Meshwork and Approach a Lesion for Functional Regeneration

Using a mouse model for ischemic stroke, investigators showed that neuroblast migration was restricted by reactive astrocytes in and around the lesion. To migrate, the neuroblasts used Slit1-Robo2 signaling to disrupt the actin cytoskeleton in reactive astrocytes at the site of contact. Slit1-overexpressing neuroblasts transplanted into the poststroke brain migrated closer to the lesion than did control neuroblasts. [Sci Adv] Full Article

Epigenetic Regulator UHRF1 Inactivates REST and Growth Suppressor Gene Expression via DNA Methylation to Promote Axon Regeneration

Scientists revealed an epigenetic mechanism that silenced gene expression by ubiquitin-like containing PHD ring finger 1 (UHRF1)-dependent DNA methylation to promote axon regeneration. They suggested that the transient increase in the transcriptional regulator regulator RE1 silencing transcription factor (REST), controlled by miR-9 and UHRF1, allowed neurons to enter a less mature state that favored a regenerative state. [Proc Natl Acad Sci USA] Abstract | Press Release

Sh3rf2 Haploinsufficiency Leads to Unilateral Neuronal Development Deficits and Autistic-Like Behaviors in Mice

The authors generated mice lacking one copy of Sh3rf2, which was detected in autism spectrum disorder (ASD) patients, to determine whether Sh3rf2 is involved in brain development and whether mutation of SH3RF2 is causative for ASD and the mechanisms linking it to ASD traits. [Cell Rep] Full Article | Graphical Abstract

Inhibitors of Ribosome Biogenesis Repress the Growth of MYCN-Amplified Neuroblastoma

Researchers showed a strong correlation between high-risk disease, MYCN expression, poor survival, and ribosome biogenesis in neuroblastoma patients. Treatment of neuroblastoma cells with quarfloxin or CX-5461, two small molecule inhibitors of RNA polymerase I, suppressed MYCN expression, induced DNA damage, and activated p53 followed by cell cycle arrest or apoptosis. [Oncogene] Full Article

Axon-Seq Decodes the Motor Axon Transcriptome and Its Modulation in Response to ALS

Investigators identified 3,500-5,000 transcripts in mouse and human stem cell-derived spinal motor axons, most of which were required for oxidative energy production and ribogenesis. Axons contained transcription factor mRNAs, e.g., Ybx1, with implications for local functions. As motor axons degenerate in ALS, the authors investigated their response to the SOD1^G93A mutation, identifying 121 ALS-dysregulated transcripts. [Stem Cell Reports] Full Article | Press Release | Graphical Abstract

MicroRNA-129-5p Is Regulated by Choline Availability and Controls EGF Receptor Synthesis and Neurogenesis in the Cerebral Cortex

Scientists found that low choline (LC) availability led to the upregulation of miR-129-5p expression in cortical neural progenitor cells (NPCs) in vitro and in vivo, causing the downregulation of epidermal growth factor (EGF) receptor and thereby disrupting NPC self-renewal and cortical neurogenesis. [FASEB J] Abstract

ALDH1A3 Induces Mesenchymal Differentiation and Serves as a Predictor for Survival in Glioblastoma

Aldehyde dehydrogenase (ALDH)1A3 was a major contributor to aldehyde dehydrogenase activity and a key driver in triggering mesenchymal transformation in glioblastoma (GBM). ALDH1A3-based molecular classification scheme could help to improve guidance for prognosis forecasting and individualized treatment decision making for GBM patients. [Cell Death Dis] Full Article

MicroRNA-128 Protects Dopamine Neurons from Apoptosis and Upregulates the Expression of Excitatory Amino Acid Transporter 4 in Parkinson’s Disease by Binding to AXIN1

In dopamine neurons, upregulated miR-128 expression or sh-axis inhibition protein 1 (AXIN1) increased the positive expression rate of amino acid transporter 4 together with mRNA and protein levels, but decreased the mRNA and protein levels of AXIN1, apoptosis rate along with the positive expression rate of AXIN1; however, the opposite trend was found in response to transfection with miR-128 inhibitors. [Cell Physiol Biochem] Full Article

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Modeling Parkinson’s Disease and Atypical Parkinsonian Syndromes Using Induced Pluripotent Stem Cells

The authors summarize recent findings from induced pluripotent stem cell-based modeling of Parkinson’s disease and several atypical parkinsonian syndromes including multiple system atrophy, frontotemporal dementia and parkinsonism linked to chromosome 17 and Perry syndrome. [Int J Mol Sci] Full Article

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AC Immune and Lilly Announce License and Collaboration Agreement

AC Immune SA and Eli Lilly and Company announced that the two companies have signed a license and collaboration agreement to research and develop tau aggregation inhibitor small molecules for the potential treatment of Alzheimer’s disease and other neurodegenerative diseases. [AC Immune SA] Press Release

Eisai and UCL Commence Preparations for Phase I Clinical Studies in Alzheimer’s Disease for Novel Anti-Tau Antibody E2814 Discovered through Joint Research

Eisai Co., Ltd. and University College London (UCL) announced that they have commenced preparations for Phase I clinical studies on E2814, the first clinical candidate from their drug discovery collaboration, in Alzheimer’s disease patients within fiscal 2018. [Eisai Co., Ltd.] Press Release

Rodin Therapeutics Announces Initiation of Phase I Clinical Trial of a Selective CoREST Inhibitor to Treat Neurologic Diseases

Rodin Therapeutics announced the initiation of a Phase I clinical trial of the company’s lead candidate, RDN-929, a potent and selective HDAC-CoREST inhibitor. [Rodin Therapeutics] Press Release

Denali Therapeutics Announces First Patient Dosed in Phase Ib Study of DNL201 for Parkinson’s Disease

Denali Therapeutics Inc. announced initiation of dosing in a Phase Ib clinical study of DNL201 in patients with Parkinson’s disease. [Denali Therapeutics Inc.] Press Release

CereSpir Incorporated and the National Neuroscience Institute Singapore Announce Positive Data Showing Beneficial Effects of CereSpir’s Clinical Stage Compound Itanapraced in a LRRK2 Model of Parkinson’s Disease

CereSpir Inc. and National Neuroscience Institute Singapore announced that they have obtained animal proof of concept for CERESPIR’s clinical stage compound itanapraced in Parkinson’s disease models. [CereSpir Inc.] Press Release

Alzheimer’s Researchers Receive Chan Zuckerberg Initiative Funding

A team of researchers at Washington University School of Medicine in St. Louis has been funded by the Chan Zuckerberg Initiative to study the root causes of neurodegenerative disorders. [Washington University School of Medicine] Press Release

Duke Trio Shares $1 Million Award to Understand Genetic Roots of Parkinson’s Disease

A trio of Duke researchers have received a grant of more than $1 million to study the role of astrocytes–common, star-shaped support cells within the brain–in the development of Parkinson’s disease. The award is part of more than $64 million in funding being given by the Chan Zuckerburg Initiative, which brings together experimental scientists from a variety of fields to better understand the root causes of neurodegenerative disorders. [Duke University] Press Release

Europe’s AI Researchers Launch Professional Body over Fears of Falling Behind

Some of Europe’s top machine-learning researchers have founded an organization to strengthen capacity in artificial intelligence (AI) technology on the continent. [Nature News] Editorial

Lawsuit Alleges NIH, FDA Let Clinical Trial Sponsors Off the Hook

A former top official at the FDA and a longtime science journalist are suing the agency and the National Institutes of Health (NIH), saying they let clinical trial sponsors off the hook for reporting nearly a decade’s worth of important scientific data. [STAT News] Editorial

NIH to Spend up to $20 Million on Search for Alternatives to Fetal Tissue for Research

The National Institutes of Health (NIH) wants to fund up to $20 million worth of research into alternatives to using human fetal tissue to study disease, the agency announced. [STAT News] Editorial

NEW 11^th American Association for Cancer Research (AACR) and Japanese Cancer Association (JCA) Joint Conference
February 8-12, 2019
Maui, Hawaii, United States

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NEW Postdoctoral Fellow – Neurotrauma and Neural Repair Mechanisms (University of Pennsylvania)

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PhD – Neuroscience (Institute for Neuroscience)

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Director – Tanz Centre for Research in Neurodegenerative Diseases (University of Toronto)

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Faculty Positions – Translational Neurosciences (Wayne State University)

Postdoctoral Scholar – Medulloblastoma (University of California, San Francisco)

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