Advances in CNS Organoids: A Focus on Organoid-Based Models for Motor Neuron Disease

Scientists review recent advances in the development of CNS organoid models, their application in neurodegenerative diseases and technical limitations.
[Tissue Engineering Part C: Methods]
Vieira de Sa, R., Canizares Luna, M., & Pasterkamp, J. (2021). Advances in CNS organoids: a focus on organoid-based models for motor neuron disease. Tissue Engineering Part C: Methods. https://doi.org/10.1089/ten.TEC.2020.0337 Cite
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Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1

Scientists present a review focusing on studies that have used iPSCs for disease modeling and drug discovery in NPC1 and draw a comparison to commonly used NPC1 models.
[International Journal of Molecular Sciences]
Völkner, C., Liedtke, M., Hermann, A., & Frech, M. J. (2021). Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1. International Journal of Molecular Sciences, 22(2), 710. https://doi.org/10.3390/ijms22020710 Cite
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BNIP3L/NIX-Mediated Mitophagy Protects Against Glucocorticoid-Induced Synapse Defects

The authors investigated the role of glucocorticoids in mitophagy inhibition and subsequent synaptic defects in hippocampal neurons, SH-SY5Y cells, and ICR mice.
[Nature Communications]
Choi, G. E., Lee, H. J., Chae, C. W., Cho, J. H., Jung, Y. H., Kim, J. S., Kim, S. Y., Lim, J. R., & Han, H. J. (2021). BNIP3L/NIX-mediated mitophagy protects against glucocorticoid-induced synapse defects. Nature Communications, 12(1), 487. https://doi.org/10.1038/s41467-020-20679-y Cite
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p53 Is Required for Nuclear but Not Mitochondrial DNA Damage-Induced Degeneration

Researchers induced selective mitochondrial DNA damage in neuronal axons using microfluidic chambers that allowed for the spatial and fluidic isolation of neuronal cell bodies from the axons.
[Cell Death & Disease]
Geden, M. J., Romero, S. E., & Deshmukh, M. (2021). p53 is required for nuclear but not mitochondrial DNA damage-induced degeneration. Cell Death & Disease, 12(1), 1–11. https://doi.org/10.1038/s41419-020-03373-1 Cite
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Role of miRNAs Shuttled by Mesenchymal Stem Cell-Derived Small Extracellular Vesicles in Modulating Neuroinflammation

Scientists identified nine miRNAs significantly dysregulated in IFN-γ-primed MSCs, but present at different levels in their derived small extracellular vesicles.
[Scientific Reports]
Giunti, D., Marini, C., Parodi, B., Usai, C., Milanese, M., Bonanno, G., Kerlero de Rosbo, N., & Uccelli, A. (2021). Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation. Scientific Reports, 11(1), 1740. https://doi.org/10.1038/s41598-021-81039-4 Cite
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Mesenchymal Stem Cell-Derived Exosome miR-542-3p Suppresses Inflammation and Prevents Cerebral Infarction

Microarray indicated a decrease of miR-542-3p and an increase of Toll-Like Receptor 4 (TLR4) in middle cerebral artery occlusion mice comparing with sham mice. And luciferase and RIP analysis indicated a binding of miR-542-3p and TLR4.
[Current Stem Cell Research & Therapy]
Cai, G., Cai, G., Zhou, H., Zhuang, Z., Liu, K., Pei, S., Wang, Y., Wang, H., Wang, X., Xu, S., Cui, C., Sun, M., Guo, S., Jia, K., Wang, X., & Zhang, D. (2021). Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction. Stem Cell Research & Therapy, 12(1), 2. https://doi.org/10.1186/s13287-020-02030-w Cite
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TNFα Promotes Oral Cancer Growth, Pain, and Schwann Cell Activation

The authors hypothesized that the oral cancer mediator TNFα activated Schwann cells, which further promoted cancer progression and pain.
[Scientific Reports]
Salvo, E., Tu, N. H., Scheff, N. N., Dubeykovskaya, Z. A., Chavan, S. A., Aouizerat, B. E., & Ye, Y. (2021). TNFα promotes oral cancer growth, pain, and Schwann cell activation. Scientific Reports, 11(1), 1840. https://doi.org/10.1038/s41598-021-81500-4 Cite
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PIAS1 Modulates Striatal Transcription, DNA Damage Repair, and SUMOylation with Relevance to Huntington’s Disease

Investigators evaluated the mechanistic contributions of protein inhibitor of activated STAT-1 (PIAS1) in Huntington’s disease (HD) mice and HD patient-derived induced pluripotent stem cells and found a link between PIAS1 and DNA damage repair pathways.
[Proceedings of the National Academy of Sciences of the United States of America]
Morozko, E. L., Smith-Geater, C., Monteys, A. M., Pradhan, S., Lim, R. G., Langfelder, P., Kachemov, M., Hill, A., Stocksdale, J. T., Cullis, P. R., Wu, J., Ochaba, J., Miramontes, R., Chakraborty, A., Hazra, T. K., Lau, A., St-cyr, S., Orellana, I., Kopan, L., … Thompson, L. M. (2021). PIAS1 modulates striatal transcription, DNA damage repair, and SUMOylation with relevance to Huntington’s disease. Proceedings of the National Academy of Sciences, 118(4). https://doi.org/10.1073/pnas.2021836118 Cite
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Current Understanding of the Molecular and Cellular Pathology of Diabetic Retinopathy

The authors highlight research that has led to a new understanding of retinal pathophysiology during diabetes mellitus and that has uncovered potential new therapeutic avenues to treat this debilitating disease.
[Nature Reviews Endocrinology]
Antonetti, D. A., Silva, P. S., & Stitt, A. W. (2021). Current understanding of the molecular and cellular pathology of diabetic retinopathy. Nature Reviews Endocrinology, 1–12. https://doi.org/10.1038/s41574-020-00451-4 Cite
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Dietary Capsaicin Normalizes CGRP Peptidergic DRG Neurons in Experimental Diabetic Peripheral Neuropathy

Researchers supplemented capsaicin in the diet of the animals to upregulate calcitonin gene-related peptide (CGRP) and reversed the downregulation of the neuropeptide in the dorsal root ganglion (DRG) neurons dissociated from the diabetic animals, via gene transfection and exogenous CGRP, to test disease-preventing and disease-limiting effects of CGRP.
[Scientific Reports]
Zhang, X.-Y., Guo, Z., Li, T.-P., & Sun, T. (2021). Dietary capsaicin normalizes CGRP peptidergic DRG neurons in experimental diabetic peripheral neuropathy. Scientific Reports, 11(1), 1704. https://doi.org/10.1038/s41598-021-81427-w Cite
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Role of miRNAs Shuttled by Mesenchymal Stem Cell-Derived Small Extracellular Vesicles in Modulating Neuroinflammation

Investigators showed that miR-467f and miR-466q modulate the pro-inflammatory phenotype of activated N9 microglia cells and of primary microglia acutely isolated from late symptomatic SOD1G93A mice, a murine ALS model, by downregulating Tnf and Il1b expression.
[Scientific Reports]
Giunti, D., Marini, C., Parodi, B., Usai, C., Milanese, M., Bonanno, G., Kerlero de Rosbo, N., & Uccelli, A. (2021). Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation. Scientific Reports, 11(1), 1740. https://doi.org/10.1038/s41598-021-81039-4 Cite
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