36 results found
    1. Neuroscience

    Loss of presenilin function is associated with a selective gain of APP function

    Carole Deyts et al.
    Amyloid precursor protein expression and accumulation of its intracellular fragment are required for exuberant neurite outgrowth associated with pathological presenilin 1 loss-of-function mutations before the emergence of amyloid burden in mice.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Pathogenic PS1 phosphorylation at Ser367

    Masato Maesako et al.
    PS1 phosphorylation at Ser367 is the potential hyperactivity-driven culprit of pathogenic change in PS1 conformation in vitro and in vivo.
    1. Neuroscience

    Presenilin/γ-secretase-dependent EphA3 processing mediates axon elongation through non-muscle myosin IIA

    Míriam Javier-Torrent et al.
    EphA signaling plays dual opposite roles on axon dynamics in neurons, so it inhibits and promotes axon growth through ligand binding and receptor processing, respectively.
    1. Cell Biology
    2. Neuroscience

    Presenilin mutations deregulate mitochondrial Ca2+ homeostasis and metabolic activity causing neurodegeneration in Caenorhabditis elegans

    Shaarika Sarasija et al.
    In C. elegans, presenilin functions, independent of its gamma-secretase proteolytic activity, to regulate mitochondrial metabolism by controlling ER-mitochondrial calcium transfer and, even in the absence of Abeta signaling, loss of this activity leads to neurodegeneration.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The amyloid-beta forming tripeptide cleavage mechanism of γ-secretase

    David M Bolduc et al.
    The protease γ-secretase generates amyloid-beta peptides using a mechanism that is driven by the stabilization of an enzyme-substrate scisson complex.
    1. Neuroscience

    Mechanisms of hyperexcitability in Alzheimer’s disease hiPSC-derived neurons and cerebral organoids vs isogenic controls

    Swagata Ghatak et al.
    Increased excitation and decreased inhibition associated with abnormal neuronal morphology, aberrant ion channel properties, and synaptic dysfunction contribute to hyperexcitability in Alzheimer’s disease hiPSC-derived neuronal cultures and cerebral organoids.
    1. Cell Biology

    Super-resolution microscopy reveals majorly mono- and dimeric presenilin1/γ-secretase at the cell surface

    Abril Angélica Escamilla-Ayala et al.
    Super-resolution microscopy sets a new strategy to comprehend the membrane organization of γ-secretase at single complex resolution identifying nanodomain associations and its diffusion in situ in the living membrane.
    1. Developmental Biology
    2. Neuroscience

    Regulation of nerve growth and patterning by cell surface protein disulphide isomerase

    Geoffrey MW Cook et al.
    The nerve growth-repellent activity that generates spinal nerve repeat-patterning in birds and mammals is identified at the molecular level, and a similar system is revealed in adult brain grey matter.
    1. Computational and Systems Biology
    2. Genetics and Genomics

    The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer’s disease mutations

    Mireia Seuma et al.
    A massively parallel analysis of the effects of mutations on amyloid beta nucleation provide the first comprehensive atlas of how mutations alter the formation of amyloid fibrils.
    1. Immunology and Inflammation
    2. Neuroscience

    Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition

    Alessio Vittorio Colombo et al.
    Experiments in a mouse model for Alzheimer’s disease using germ-free and conventionally housed animals reveal that microbiota-derived short-chain fatty acids promote the deposition of cerebral Aβ plaques.

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