The role of colony-stimulating factor 1 receptor (CSF1R) signaling in microglial homeostasis in the adult brain is largely unknown. To this end, researchers tested the effects of selective CSF1R inhibitors on microglia in adult mice. Surprisingly, extensive treatment results in elimination of approximately 99% of all microglia brain-wide, showing that microglia in the adult brain are physiologically dependent upon CSF1R signaling. [Neuron]
Abstract | Press Release Conditions and Constraints for Astrocyte Calcium Signaling in the Hippocampal Mossy Fiber Pathway
Investigators used genetically encoded Ca2+ and glutamate indicators as well as pharmacogenetic and electrical control of neurotransmitter release to explore astrocyte activity in the hippocampal mossy fiber pathway. [Neuron] Abstract | Press Release
Pharmacological Chaperones Stabilize Retromer to Limit APP Processing
The authors determined whether pharmacological chaperones can enhance retromer stability and function. An in vitro assay identified one molecule that stabilized retromer against thermal denaturation. They turned to cultured hippocampal neurons, showing that this small molecule increases the levels of retromer proteins, shifts amyloid-precursor protein (APP) away from the endosome, and decreases the pathogenic processing of APP. [Nat Chem Biol] Abstract | Press Release
Enhancing Adult Nerve Regeneration through the Knockdown of Retinoblastoma Protein
Researchers described a role for the retinoblastoma (Rb) protein, widely expressed in adult sensory neurons and their axons, during regeneration. In adult sensory neurons, Rb short interfering RNA knockdown or Rb1 deletion in vitro enhances neurite outgrowth and branching. [Nat Commun] Abstract | Press Release
MHC-I Expression Renders Catecholaminergic Neurons Susceptible to T-Cell-Mediated Degeneration
Researchers provide evidence from immunolabel, RNA expression and mass spectrometry analysis of postmortem samples that human catecholaminergic substantia nigra and locus coeruleus neurons express MHC-I, and that this molecule is inducible in human stem cell-derived dopamine neurons. [Nat Commun] Abstract | Press Release
TRF2-Mediated Stabilization of hREST4 Is Critical for the Differentiation and Maintenance of Neural Progenitors
Researchers found that the telomere repeat binding factor 2 (TRF2)-mediated counterbalance between human Repressor Element-1 Silencing Transcription Factor 4 (hREST4) and REST is vital for both the generation and maintenance of neural progenitor cells, suggesting an important role for TRF2 in both neurogenesis and function of the central nervous system. [Stem Cells] Abstract
A PCNA-Derived Cell Permeable Peptide Selectively Inhibits Neuroblastoma Cell Growth
Scientists designed a cell permeable peptide containing the proliferating cell nuclear antigen (PCNA) L126-Y133 sequence. They report that this peptide selectively kills human neuroblastoma cells, especially those with MYCN gene amplification, with much less toxicity to non-malignant human cells. [PLoS One]
Full Article | Press Release
Neural Stem Cells Genetically-Modified to Express Neprilysin Reduce Pathology in Alzheimer Transgenic Models
Findings revealed that stem cell-mediated delivery of neprilysin provides marked and significant reductions in beta-amyloid (Aβ) pathology and increases synaptic density in both 3xTg-Alzheimer’s disease and Thy1-APP transgenic mice. Remarkably, Aβ plaque loads are reduced not only in the hippocampus and subiculum adjacent to engrafted neural stem cells, but also within the amygdala and medial septum, areas that receive afferent projections from the engrafted region. [Stem Cell Res Ther] Full Article | Press Release