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    1. Cell Biology
    2. Neuroscience

    Amphiphysin I cleavage by asparagine endopeptidase leads to tau hyperphosphorylation and synaptic dysfunction

    Xingyu Zhang et al.
    Amphiphysin I is identified as a new substrate of AEP, and the resultant fragment induces synaptic dysfunction and promotes tau hyperphosphorylation via activating CDK5 kinase.
    1. Neuroscience

    Cytosolic calcium regulates cytoplasmic accumulation of TDP-43 through Calpain-A and Importin α3

    Jeong Hyang Park et al.
    Genetic and optogenetic analyses in Drosophila neurons reveal calcium as one of the key regulators of nucleocytoplasmic localization of TDP-43 via Calpain-A and Importin α3.
    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.
    1. Cell Biology

    Impaired lysosomal acidification triggers iron deficiency and inflammation in vivo

    King Faisal Yambire et al.
    Impaired lysosomal acidification results in retention of iron inside lysosomes, triggering functional iron deficiency, dysfunctional mitochondria (especially mtDNA loss), and inflammation in vivo in a mouse model of lysosomal disease.
    1. Cell Biology

    Nuclear export of misfolded SOD1 mediated by a normally buried NES-like sequence reduces proteotoxicity in the nucleus

    Yongwang Zhong et al.
    Cellular and genetic approaches reveal that exposure of a normally buried nuclear export signal (NES)-like sequence mediates export of ALS-linked mutant and misfolded wild-type SOD1 to the cytoplasm by CRM1.
    1. Neuroscience

    Suppression of C9orf72 RNA repeat-induced neurotoxicity by the ALS-associated RNA-binding protein Zfp106

    Barbara Celona et al.
    Zfp106 functions as an RNA binding protein, binds directly to GGGGCC RNA repeats, is required in motor neurons to prevent ALS-like neurodegeneration in mice, and can suppress neurotoxicity in an established fly model of ALS.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Multiple pathways of toxicity induced by C9orf72 dipeptide repeat aggregates and G4C2 RNA in a cellular model

    Frédéric Frottin et al.
    Protein aggregates resulting from mutations in C9orf72 impair different aspects of cellular quality control in the cytosol and the nucleus, but mRNA-mediated effects contribute more strongly to toxicity.
    1. Neuroscience

    Seizures are a druggable mechanistic link between TBI and subsequent tauopathy

    Hadeel Alyenbaawi et al.
    A traumatic brain injury model is invented for larval zebrafish and applied to a new fluorescent 'tauopathy reporter fish', revealing a role for seizures in progression towards dementias.
    1. Cell Biology
    2. Neuroscience

    Phagocytic glia are obligatory intermediates in transmission of mutant huntingtin aggregates across neuronal synapses

    Kirby M Donnelly et al.
    Prion-like transfer of mutant huntingtin aggregates from presynaptic to postsynaptic neurons is enhanced by neuronal silencing and requires passage through the cytoplasm of Draper-expressing phagocytic glia in adult Drosophila brains.
    1. Biochemistry and Chemical Biology

    Nicotinamide mononucleotide adenylyltransferase uses its NAD+ substrate-binding site to chaperone phosphorylated Tau

    Xiaojuan Ma et al.
    Mechanistic insight into the chaperone-like activity of NMNAT to phosphorylated Tau reveals a connection between NAD+metabolism and Tau homeostasis.