45 results found
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Targeted degradation of aberrant tau in frontotemporal dementia patient-derived neuronal cell models

    M Catarina Silva et al.
    A new Cereblon-recruiting bifunctional tau ligand, QC-01-175, promotes aberrant tau degradation and rescue of stress vulnerability in human neuronal cell models of tauopathy.
    1. Cell Biology
    2. Neuroscience

    Frontotemporal dementia mutant Tau promotes aberrant Fyn nanoclustering in hippocampal dendritic spines

    Pranesh Padmanabhan et al.
    Super-resolution imaging reveals that the microtubule-associated protein Tau regulates the Fyn kinase organisation in dendrites, and that the frontotemporal dementia mutant Tau promotes aberrant Fyn clustering, potentially leading to synaptic dysfunction.
    1. Biochemistry and Chemical Biology
    2. Human Biology and Medicine

    RNA-Binding Proteins: A matter of balance

    Aaron D Gitler, John D Fryer
    New analyses shift the view that some forms of amyotrophic lateral sclerosis and frontotemporal dementia are due to defects in a single RNA-binding protein.
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    1. Biochemistry and Chemical Biology
    2. Human Biology and Medicine

    Unexpected similarities between C9ORF72 and sporadic forms of ALS/FTD suggest a common disease mechanism

    Erin G Conlon et al.
    Idiopathic patients along a complex motor neuron disease-dementia spectrum exhibit mRNA splicing changes that are due to multi-protein insolubility.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Multiplex image-based autophagy RNAi screening identifies SMCR8 as ULK1 kinase activity and gene expression regulator

    Jennifer Jung et al.
    An image-based multiplex autophagosome RNAi screen targeting all Rab GTPases as well as their GAPs and GEFs identifies the Rab GEF SMCR8 as multifaceted autophagy modulator, which regulates kinase activity and gene expression of ULK1.
    1. Neuroscience

    Functional gradients of the cerebellum

    Xavier Guell et al.
    Cerebellar functional regions follow a gradual organization, which progresses from primary (motor) to transmodal (Default Mode Network) regions, and a secondary axis extends from task-unfocused to task-focused processing.
    1. Chromosomes and Gene Expression
    2. Neuroscience

    Activation of GCN2 kinase by ribosome stalling links translation elongation with translation initiation

    Ryuta Ishimura et al.
    Activation of the integrated stress response by stalled translation elongation complexes attenuates neurodegeneration, and demonstrates a protective link between a decrease in the rate of translation initiation and defects in translation elongation.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Cell Biology
    2. Neuroscience

    Degradation of engulfed mitochondria is rate-limiting in Optineurin-mediated mitophagy in neurons

    Chantell S Evans, Erika LF Holzbaur
    In neuronal mitophagy, Parkin and OPTN induce efficient sequestration of damaged somal mitochondria into autophagosomes, but slow turnover via lysosomal acidification may be a point of vulnerability for the cell.

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