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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Loss of POMC-Mediated Antinociception Contributes to Painful Diabetic Neuropathy

Scientists report dysfunctional proopiomelanocortin (POMC)-mediated antinociception in sensory neurons in diabetes.
[Scientific Reports]
Deshpande, D., Agarwal, N., Fleming, T., Gaveriaux-Ruff, C., Klose, C. S. N., Tappe-Theodor, A., Kuner, R., & Nawroth, P. (2021). Loss of POMC-mediated antinociception contributes to painful diabetic neuropathy. Nature Communications, 12(1), 426. https://doi.org/10.1038/s41467-020-20677-0 Cite
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Histone Demethylase KDM4C Controls Tumorigenesis of Glioblastoma by Epigenetically Regulating p53 and C-Myc

Researchers showed that KDM4C knockdown significantly repressed proliferation and tumorigenesis of glioblastoma cells in vitro and in vivo that were rescued by overexpressing wild-type KDM4C but not a catalytic dead mutant.
[Cell Death & Disease]
Lee, D. H., Kim, G. W., Yoo, J., Lee, S. W., Jeon, Y. H., Kim, S. Y., Kang, H. G., Kim, D.-H., Chun, K.-H., Choi, J., & Kwon, S. H. (2021). Histone demethylase KDM4C controls tumorigenesis of glioblastoma by epigenetically regulating p53 and c-Myc. Cell Death & Disease, 12(1), 1–14. https://doi.org/10.1038/s41419-020-03380-2 Cite
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Integrated, Automated Maintenance, Expansion and Differentiation of 2D and 3D Patient-Derived Cellular Models for High Throughput Drug Screening

Scientists provided automated protocols for neuronal differentiation of neural progenitor cells in 2D culture and 3D midbrain organoids for high throughput screenings.
[Scientific Reports]
Boussaad, I., Cruciani, G., Bolognin, S., Antony, P., Dording, C. M., Kwon, Y.-J., Heutink, P., Fava, E., Schwamborn, J. C., & Krüger, R. (2021). Integrated, automated maintenance, expansion and differentiation of 2D and 3D patient-derived cellular models for high throughput drug screening. Scientific Reports, 11(1), 1439. https://doi.org/10.1038/s41598-021-81129-3 Cite
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Transneuronal Delivery of Hyper-Interleukin-6 Enables Functional Recovery after Severe Spinal Cord Injury in Mice

The authors report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This was achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6, a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration.
[Nature Communications]
Transneuronal delivery of hyper-interleukin-6 enables functional recovery after severe spinal cord injury in mice | Nature Communications. (n.d.). Retrieved January 15, 2021, from https://www.nature.com/articles/s41467-020-20112-4 Cite
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O-GlcNAcylation Ameliorates the Pathological Manifestations of Alzheimer’s Disease by Inhibiting Necroptosis

The authors found that O-GlcNAcylation plays a protective role in Alzheimer’s disease by inhibiting necroptosis.
[Science Advances]
Park, J., Ha, H.-J., Chung, E. S., Baek, S. H., Cho, Y., Kim, H. K., Han, J., Sul, J. H., Lee, J., Kim, E., Kim, J., Yang, Y. R., Park, M., Kim, S. H., Arumugam, T. V., Jang, H., Seo, S. W., Suh, P.-G., & Jo, D.-G. (2021). O-GlcNAcylation ameliorates the pathological manifestations of Alzheimer’s disease by inhibiting necroptosis. Science Advances, 7(3), eabd3207. https://doi.org/10.1126/sciadv.abd3207 Cite
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A Subset of Spinal Dorsal Horn Interneurons Crucial for Gating Touch-Evoked Pain-Like Behavior

Scientists identified a subset of inhibitory interneurons in the spinal dorsal horn (SDH) operated by adeno-associated viral vectors incorporating a neuropeptide Y promoter (AAV-NpyP+) and showed that specific ablation or silencing of AAV-NpyP+ SDH interneurons converted touch-sensing Aβ fiber-derived signals to morphine-resistant pain-like behavioral responses.
[Proceedings of the National Academy of Sciences of the United States of America]
Tashima, R., Koga, K., Yoshikawa, Y., Sekine, M., Watanabe, M., Tozaki-Saitoh, H., Furue, H., Yasaka, T., & Tsuda, M. (2021). A subset of spinal dorsal horn interneurons crucial for gating touch-evoked pain-like behavior. Proceedings of the National Academy of Sciences, 118(3). https://doi.org/10.1073/pnas.2021220118 Cite
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BlueRock Therapeutics in Collaboration with Memorial Sloan Kettering Cancer Center Receives IND Clearance for DA01 in Parkinson’s Disease

BlueRock Therapeutics, in collaboration with Memorial Sloan Kettering Cancer Center, announced that the US FDA has cleared their Investigational New Drug application to proceed with a Phase I study in patients with advanced Parkinson’s disease (PD). This is the first trial in the US to study pluripotent stem cell-derived dopaminergic neurons in patients with Parkinson’s disease.
[BlueRock Therapeutics (PR Newswire, Inc.)]
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