Using a model of cutaneous allergen exposure, investigators showed that allergens directly activated TRPV1+ sensory neurons leading to itch and pain behaviors.
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Perner, C., Flayer, C. H., Zhu, X., Aderhold, P. A., Dewan, Z. N. A., Voisin, T., Camire, R. B., Chow, O. A., Chiu, I. M., & Sokol, C. L. (2020). Substance P Release by Sensory Neurons Triggers Dendritic Cell Migration and Initiates the Type-2 Immune Response to Allergens. Immunity, 0(0). https://doi.org/10.1016/j.immuni.2020.10.001 Cite
Scientists showed that three transcription factors, Ascl1, Brn3b, and Isl1, efficiently converted fibroblasts into RGC-like neurons (iRGCs). The competence of cells to enter iRGC reprogramming route was determined by the cell-cycle status at a very early stage of the process.
[Stem Cell Reports]
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Catalent and BrainStorm Cell Therapeutics, Inc announced an agreement for the manufacture of NurOwn®, BrainStorm’s autologous cellular therapy being investigated for the treatment of ALS, also known as Lou Gehrig’s disease or motor neuron disease.
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The authors identified and isolated human iPSC-dopamine neurons with a TH-RFP reporter. Using liquid extraction surface analysis (LESA) coupled with high-resolution mass spectrometry they developed a high-throughput method for untargeted single cell lipid profiling.
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Snowden, S. G., Fernandes, H. J. R., Kent, J., Foskolou, S., Tate, P., Field, S. F., Metzakopian, E., & Koulman, A. (2020). Development and application of high-throughput single cell lipid profiling: a study of SNCA-A53T human dopamine neurons. IScience, 0(0). https://doi.org/10.1016/j.isci.2020.101703 Cite
The spheroids used were composed of six brain cell types: Astrocytes, pericytes, endothelial cells, microglia cells, oligodendrocytes, and neurons. They formed an in vitro blood brain barrier that regulated the transport of compounds into the spheroid.
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Scientists found that Dynamin-related protein 1 was dephosphorylated in several ALS models, including those with SOD1 and TDP-43 mutations, and the dephosphorylation was mediated by the pathological induction of protein phosphatase 1 activity in these models.
[Cell Death & Disease]
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Choi, S. Y., Lee, J.-H., Chung, A.-Y., Jo, Y., Shin, J., Park, H.-C., Kim, H., Lopez-Gonzalez, R., Ryu, J. R., & Sun, W. (2020). Prevention of mitochondrial impairment by inhibition of protein phosphatase 1 activity in amyotrophic lateral sclerosis. Cell Death & Disease, 11(10), 1–15. https://doi.org/10.1038/s41419-020-03102-8 Cite
A highly pleiotropic and context-dependent nature of Pin1 functional activity, strictly dependent on the phosphorylation patterns of its cellular targets, clearly emerges. In the nervous system, Pin1 is fundamental both for embryonic development and cellular homeostasis in adult neurons, due to its role as regulator of cell death and survival.
Researchers found that knockdown of CMTR1 impaired dendrite development independent of secretory cytokines and RIG-I signaling.
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Researchers determined that the Siah2 E3 ubiquitin ligase functions in a coincidence detection circuit linking responses to the Shh mitogen and the ECM to control cerebellar granule neurons germinal zone occupancy.
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The authors focus on brain microenvironment features impacted by tumor biology. They also discuss limits of current preclinical models and how complementary models, such as humanized animals and organoids, will allow deeper mechanistic insights on cancer biology, allowing for more efficient testing of therapeutic strategies, including immunotherapy, for brain cancers.
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Scientists investigated the expression and function of SRPK family members in human pluripotent stem cells and the brain. SRPK1, SRPK2, and RNF12 were expressed in human iPSCs, and quantitative total proteomic analysis confirmed the expression of these components and REX1.
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Bustos, F., Segarra-Fas, A., Nardocci, G., Cassidy, A., Antico, O., Davidson, L., Brandenburg, L., Macartney, T. J., Toth, R., Hastie, C. J., Moran, J., Gourlay, R., Varghese, J., Soares, R. F., Montecino, M., & Findlay, G. M. (2020). Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.09.025 Cite