Familial Alzheimer’s Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis

Expression data from developmental and adult neurogenesis showed relative enrichment of Notch and γ-secretase expression in stem cells, whereas expression of APP and β-secretase was enriched in neurons.
[Cell Reports]
Arber, C., Lovejoy, C., Harris, L., Willumsen, N., Alatza, A., Casey, J. M., Lines, G., Kerins, C., Mueller, A. K., Zetterberg, H., Hardy, J., Ryan, N. S., Fox, N. C., Lashley, T., & Wray, S. (2021). Familial Alzheimer’s Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis. Cell Reports, 34(2). https://doi.org/10.1016/j.celrep.2020.108615 Cite
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Differential Contribution of Transcriptomic Regulatory Layers in the Definition of Neuronal Identity

Scientists generated profiles for the three regulatory layers from developmentally and regionally distinct subpopulations of neurons from the mouse hippocampus and broader nervous system.
[Nature Communications]
Ha, K. C. H., Sterne-Weiler, T., Morris, Q., Weatheritt, R. J., & Blencowe, B. J. (2021). Differential contribution of transcriptomic regulatory layers in the definition of neuronal identity. Nature Communications, 12(1), 335. https://doi.org/10.1038/s41467-020-20483-8 Cite
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Ascending Dorsal Column Sensory Neurons Respond to Spinal Cord Injury and Downregulate Genes Related to Lipid Metabolism

Using RNA sequencing of dorsal root ganglion, researchers determined that thoracic spinal cord injury elicited a transcriptional response distinct from sciatic nerve injury.
[Scientific Reports]
Ewan, E. E., Avraham, O., Carlin, D., Gonçalves, T. M., Zhao, G., & Cavalli, V. (2021). Ascending dorsal column sensory neurons respond to spinal cord injury and downregulate genes related to lipid metabolism. Scientific Reports, 11(1), 374. https://doi.org/10.1038/s41598-020-79624-0 Cite
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Molecular Characterization of Selectively Vulnerable Neurons in Alzheimer’s Disease

To identify and characterize selectively vulnerable neuronal populations, the authors used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus—brain regions where neurofibrillary inclusions and neuronal loss occurred early and late in Alzheimer’s disease (AD), respectively—from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology.
[Nature Neuroscience]
Leng, K., Li, E., Eser, R., Piergies, A., Sit, R., Tan, M., Neff, N., Li, S. H., Rodriguez, R. D., Suemoto, C. K., Leite, R. E. P., Ehrenberg, A. J., Pasqualucci, C. A., Seeley, W. W., Spina, S., Heinsen, H., Grinberg, L. T., & Kampmann, M. (2021). Molecular characterization of selectively vulnerable neurons in Alzheimer’s disease. Nature Neuroscience, 1–12. https://doi.org/10.1038/s41593-020-00764-7 Cite
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CRISPR/Cas9 Directed to the Ube3a Antisense Transcript Improves Angelman Syndrome Phenotype in Mice

Scientists showed that gene editing of Ube3a-ATS in the mouse brain resulted in the formation of base pair insertions/deletions in neurons and the subsequent unsilencing of the paternal Ube3a allele in neurons, which partially corrected the behavior phenotype of a murine Angelman syndrome model.
[Journal of Clinical Investigation]
Schmid, R. S., Deng, X., Panikker, P., Msackyi, M., Breton, C., & Wilson, J. M. (2021). CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI142574 Cite
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Mass Generation, Neuron Labeling, and 3D Imaging of Minibrains

Scientists present a step-by-step methodology to generate human minibrain nurseries and novel strategies to subsequently label projection neurons, perform immunohistochemistry and 3D imaging of the minibrains at large multiplexable scales.
[Frontiers in Bioengineering and Biotechnology]
Govindan, S., Batti, L., Osterop, S. F., Stoppini, L., & Roux, A. (2021). Mass Generation, Neuron Labeling, and 3D Imaging of Minibrains. Frontiers in Bioengineering and Biotechnology, 8. https://doi.org/10.3389/fbioe.2020.582650 Cite
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A Three-Dimensional In Vitro Model of the Peripheral Nervous System

Scientists present an in vitro model of the peripheral nervous system by establishing a coculture model of motor neurons and Schwann cells in a 3D environment in a microengineered extracellular matrix hydrogel scaffold.
[NPG Asia Materials]
Park, S. E., Ahn, J., Jeong, H.-E., Youn, I., Huh, D., & Chung, S. (2021). A three-dimensional in vitro model of the peripheral nervous system. NPG Asia Materials, 13(1), 1–11. https://doi.org/10.1038/s41427-020-00273-w Cite
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A Capsaicinoid-Based Soft Drug, AG1529, for Attenuating TRPV1-Mediated Histaminergic and Inflammatory Sensory Neuron Excitability

Researchers report that AG1529 competitively blocked capsaicin-evoked activation of human TRPV1 with micromolar potency, moderately affected pH-induced gating, and did not alter voltage- and heat-mediated responses.
[Scientific Reports]
Nikolaeva-Koleva, M., Butron, L., González-Rodríguez, S., Devesa, I., Valente, P., Serafini, M., Genazzani, A. A., Pirali, T., Ballester, G. F., Fernández-Carvajal, A., & Ferrer-Montiel, A. (2021). A capsaicinoid-based soft drug, AG1529, for attenuating TRPV1-mediated histaminergic and inflammatory sensory neuron excitability. Scientific Reports, 11(1), 246. https://doi.org/10.1038/s41598-020-80725-z Cite
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Valproic Acid-Exposed Astrocytes Impair Inhibitory Synapse Formation and Function

Investigators examined whether exposure of cultured astrocytes to valproic acid altered neuronal morphology and synapse function of co-cultured neurons.
[Scientific Reports]
Valproic acid-exposed astrocytes impair inhibitory synapse formation and function | Scientific Reports. (n.d.). Retrieved January 8, 2021, from https://www.nature.com/articles/s41598-020-79520-7 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, LLC. announced that the FDA has cleared their Investigational New Drug (IND) application to proceed with a Phase I study in patients with advanced Parkinson’s disease (PD). This is the first trial in the United States to study pluripotent stem cell-derived dopaminergic neurons in patients with PD.
[BlueRock Therapeutics, LLC.]
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ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism

The authors describe a detrimental role of ApoE4 in regulating fatty acid (FA) metabolism across neuron and astrocyte in tandem with their distinctive mitochondrial phenotypes. ApoE4 disrupted neuronal function by decreasing FA sequestering in lipid droplets.
[Cell Reports]
Qi, G., Mi, Y., Shi, X., Gu, H., Brinton, R. D., & Yin, F. (2021). ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism. Cell Reports, 34(1). https://doi.org/10.1016/j.celrep.2020.108572 Cite
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