Extreme Vulnerability of IDH1 Mutant Cancers to NAD+ Depletion Scientists found that 2-hydroxyglutarate depletion did not inhibit growth of several IDH1 mutant solid cancer types. To identify other metabolic therapeutic targets, they systematically profiled metabolites in endogenous IDH1 mutant cancer cells after mutant IDH1 inhibition and discovered a profound vulnerability to depletion of the coenzyme NAD+. [Cancer Cell] Abstract | Graphical Abstract | Press Release Purification and Characterization of Progenitor and Mature Human Astrocytes Reveals Transcriptional and Functional Differences with Mouse Researchers report the development of an immunopanning method to acutely purify astrocytes from fetal, juvenile, and adult human brains and to maintain these cells in serum-free cultures. [Neuron] Full Article | Press Release Wallerian Degeneration Is Executed by an NMN-SARM1-Dependent Late Ca2+ Influx but Only Modestly Influenced by Mitochondria Researchers showed, in vitro and in vivo, that axotomy leads to a late increase in intra-axonal Ca2+, abolished by pharmacological or genetic reduction of NMN levels. [Cell Rep] Full Article | Graphical Abstract | Press Release Regulation of Shootin1 Gene Expression Involves NGF-induced Alternative Splicing during Neuronal Differentiation of PC12 Cells The authors demonstrated that the isoform-1 and isoform-2 of shootin1 is differentially expressed during neuronal differentiation. By blocking individual downstream pathways of NGF signaling, they found that PI3K/Akt pathway plays a major role in the expression of shootin1 isoform-2. [Sci Rep] Full Article Efficient Generation of Region-Specific Forebrain Neurons from Human Pluripotent Stem Cells under Highly Defined Condition Investigators provided an optimized paradigm to generate region-specific forebrain neurons from human pluripotent stem cells (hPSCs) under a defined system. They assessed five conditions and found that a vitronectin-coated substrate was the most efficient method to differentiate hPSCs to neurons and astrocytes. [Sci Rep] Full Article Genomic Analysis Reveals Disruption of Striatal Neuronal Development and Therapeutic Targets in Human Huntington’s Disease Neural Stem Cells Scientists utilized induced pluripotent stem cells (iPSCs) derived from Huntington’s disease (HD) patients as a human model of HD and determined that the disease phenotypes only manifest in the differentiated neural stem cell stage, not in iPSCs. [Stem Cell Rep] Full Article | Graphical Abstract Activation of AKT1/GSK-3β/β-Catenin–TRIM11/Survivin Pathway by Novel GSK-3β Inhibitor Promotes Neuron Cell Survival: Study in Differentiated SH-SY5Y Cells in OGD Model The authors aimed to elucidate the effect of a new glycogen synthase kinase-3β (GSK-3β) inhibitor in RA differentiated SH-SY5Y cells in oxygen and glucose deprivation (OGD) model. [Mol Neurobiol] Abstract Deficiency of Neuronal p38α-MAPK Attenuates Amyloid Pathology in Alzheimer’s Mouse and Cell Models through Facilitating Lysosomal Degradation of BACE1 Using immunological and biochemical methods, the authors observed that reduction of p38α-MAPK expression facilitated the lysosomal degradation of BACE1, decreased BACE1 protein and activity, and subsequently attenuated amyloid β generation in the Alzheimer’s disease mouse brain. Inhibition of p38α-MAPK also enhanced autophagy. [J Biol Chem] Abstract | Full Article miR-22 Inhibits the Proliferation, Motility, and Invasion of Human Glioblastoma Cells by Directly Targeting SIRT1 Researchers carried out gene transfection, western blot, and reverse transcription PCR to explore the role of microRNA (miR)-22 in glioblastoma tissues and cell lines. They verified that the expression of miR-22 was downregulated in glioblastoma tissues and cells rather than matched non-tumor tissues and normal human astrocyte cells. [Tumor Biol] Abstract |