The Melanoma Brain Metastatic Microenvironment: Aldolase C Partakes in Shaping the Malignant Phenotype of Melanoma Cells – A Case of Inter-Tumor Heterogeneity

Researchers used brain metastasizing variants from three human melanomas to explore the functional role of Aldolase C in the formation and maintenance of melanoma brain metastasis.
[Molecular Oncology]
Izraely, S., Ben‐Menachem, S., Sagi‐Assif, O., Meshel, T., Malka, S., Telerman, A., Bustos, M. A., Ramos, I. R., Pasmanik‐Chor, M., Hoon, D. S. B., & Witz, I. P. (n.d.). The melanoma brain metastatic microenvironment: Aldolase C partakes in shaping the malignant phenotype of melanoma cells - A case of inter-tumor heterogeneity. Molecular Oncology, n/a(n/a). https://doi.org/https://doi.org/10.1002/1878-0261.12872 Cite
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Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions

Scientists summarize the known ultrastructural, molecular, and functional features of direct microglia-neuron interactions and their roles in brain disease.
[Neuron]
Cserép, C., Pósfai, B., & Dénes, Á. (2020). Shaping Neuronal Fate: Functional Heterogeneity of Direct Microglia-Neuron Interactions. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2020.11.007 Cite
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The NLRP3 Inflammasome Inhibitor OLT1177 Rescues Cognitive Impairment in a Mouse Model of Alzheimer’s Disease

Scientists analyzed the effect of pharmacological inhibition of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome using dapansutrile (OLT1177), an oral NLRP3-specific inhibitor that is safe in humans.
[Proceedings of the National Academy of Sciences of the United States of America]
Lonnemann, N., Hosseini, S., Marchetti, C., Skouras, D. B., Stefanoni, D., D’Alessandro, A., Dinarello, C. A., & Korte, M. (2020). The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2009680117 Cite
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Single Cell RNA Sequencing of Human Microglia Uncovers a Subset Associated with Alzheimer’s Disease

Scientists investigated the population structure of live microglia purified from human cerebral cortex samples obtained at autopsy and during neurosurgical procedures.
[Nature Communications]
Olah, M., Menon, V., Habib, N., Taga, M. F., Ma, Y., Yung, C. J., Cimpean, M., Khairallah, A., Coronas-Samano, G., Sankowski, R., Grün, D., Kroshilina, A. A., Dionne, D., Sarkis, R. A., Cosgrove, G. R., Helgager, J., Golden, J. A., Pennell, P. B., Prinz, M., … De Jager, P. L. (2020). Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease. Nature Communications, 11(1), 6129. https://doi.org/10.1038/s41467-020-19737-2 Cite
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Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes

Scientists focus on recent findings on extracellular vesicle-mediated bilateral crosstalk, between glioblastoma cells and astrocytes, highlighting the protumor and antitumor roles of astrocytes in glioblastoma development.
[Trends in Neuroscience]
Nieland, L., Morsett, L. M., Broekman, M. L. D., Breakefield, X. O., & Abels, E. R. (2020). Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes. Trends in Neurosciences, 0(0). https://doi.org/10.1016/j.tins.2020.10.014 Cite
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Role of RPTPβ/ζ in Neuroinflammation and Microglia-Neuron Communication

Investigators tested if RPTPβ/ζ was involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTPβ/ζ.
[Scientific Reports]
Fernández-Calle, R., Galán-Llario, M., Gramage, E., Zapatería, B., Vicente-Rodríguez, M., Zapico, J. M., de Pascual-Teresa, B., Ramos, A., Ramos-Álvarez, M. P., Uribarri, M., Ferrer-Alcón, M., & Herradón, G. (2020). Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication. Scientific Reports, 10(1), 20259. https://doi.org/10.1038/s41598-020-76415-5 Cite
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CSF1R Inhibition Depletes Tumor-Associated Macrophages and Attenuates Tumor Progression in a Mouse Sonic Hedgehog-Medulloblastoma Model

By combining longitudinal manganese-enhanced magnetic resonance imaging and immune profiling of a sporadic mouse model of SHH-MB, researchers found the density of TAMs was higher in the ~50% of tumors that progress to lethal disease.
[Oncogene]
CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model | Oncogene. (n.d.). Retrieved November 7, 2020, from https://www.nature.com/articles/s41388-020-01536-0 Cite
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Neuroprotective versus Neuroinflammatory Roles of Complement: From Development to Disease

Complement proteins are ancient components of innate immunity that have emerged as crucial regulators of neural networks. Investigators discuss these roles in the context of the CNS development, acute CNS viral infections, and post-infectious and noninfectious CNS disorders, with an emphasis on microglia-mediated loss of synapses.
[Trends in Neurosciences]
Kanmogne, M., & Klein, R. S. (2020). Neuroprotective versus Neuroinflammatory Roles of Complement: From Development to Disease. Trends in Neurosciences, 0(0). https://doi.org/10.1016/j.tins.2020.10.003 Cite
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Common Schizophrenia Risk Variants Are Enriched in Open Chromatin Regions of Human Glutamatergic Neurons

Scientists found that chromatin accessibility varied greatly by cell type and, more moderately, by brain region, with glutamatergic neurons showing the largest regional variability.
[Nature Communications]
Hauberg, M. E., Creus-Muncunill, J., Bendl, J., Kozlenkov, A., Zeng, B., Corwin, C., Chowdhury, S., Kranz, H., Hurd, Y. L., Wegner, M., Børglum, A. D., Dracheva, S., Ehrlich, M. E., Fullard, J. F., & Roussos, P. (2020). Common schizophrenia risk variants are enriched in open chromatin regions of human glutamatergic neurons. Nature Communications, 11(1), 5581. https://doi.org/10.1038/s41467-020-19319-2 Cite
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Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia

The authors found that, in injured optic nerves, oligodendrocyte precursor cells undergone transient proliferation but failed to differentiate into mature myelination-competent oligodendrocytes, reminiscent of what was observed in human progressive multiple sclerosis.
[Neuron]
Wang, J., He, X., Meng, H., Li, Y., Dmitriev, P., Tian, F., Page, J. C., Lu, Q. R., & He, Z. (2020). Robust Myelination of Regenerated Axons Induced by Combined Manipulations of GPR17 and Microglia. Neuron, 0(0). https://doi.org/10.1016/j.neuron.2020.09.016 Cite
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Gene Expression and Functional Deficits Underlie TREM2-Knockout Microglia Responses in Human Models of Alzheimer’s Disease

Scientists profiled microglia differentiated from isogenic, CRISPR-modified TREM2-knockout induced pluripotent stem cell lines.
[Nature Communications]
Gene expression and functional deficits underlie TREM2-knockout microglia responses in human models of Alzheimer’s disease | Nature Communications. (n.d.). Retrieved October 23, 2020, from https://www.nature.com/articles/s41467-020-19227-5 Cite
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