35 results found
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of alpha-synuclein fibrils

    Ricardo Guerrero-Ferreira et al.
    The alpha-synuclein fibril structure reported here buries residues 50-57 at the interface between its two protofilaments, suggesting that familial Parkinson's disease associated mutations in these residues lead to a structure not compatible with the one presented here.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    Two new polymorphic structures of human full-length alpha-synuclein fibrils solved by cryo-electron microscopy

    Ricardo Guerrero-Ferreira et al.
    Two new polymorphic structures of recombinant human alpha-synuclein fibrils show striking differences to previous structures, while familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
    1. Neuroscience

    TRIM28 regulates the nuclear accumulation and toxicity of both alpha-synuclein and tau

    Maxime WC Rousseaux et al.
    Convergent screens targeting the levels of alpha-synuclein and tau identify TRIM28 as a driver of their stability, nuclear accumulation and subsequent toxicity.
    1. Structural Biology and Molecular Biophysics

    Molecular basis for N-terminal alpha-synuclein acetylation by human NatB

    Sunbin Deng et al.
    The cryo-EM structure of the human N-terminal acetyltransferase NatB bound to a cognate N-terminal alpha-synuclein peptide reveals the molecular determinants of NatB-specific protein acetylation.
    1. Biochemistry and Chemical Biology
    2. Genetics and Genomics

    Therapeutic genetic variation revealed in diverse Hsp104 homologs

    Zachary M March et al.
    Exploring natural Hsp104 variation reveals unexpected tuning of a passive activity that inhibits aggregation of specific substrates to selectively counter TDP-43 or alpha-synuclein proteotoxicity connected to neurodegenerative disease.
    1. Biochemistry and Chemical Biology

    Inhibition of synucleinopathic seeding by rationally designed inhibitors

    Smriti Sangwan et al.
    Inhibitors of seeded propagation of alpha-synuclein may be developed into diagnostics and therapeutics for Parkinson's disease.
    1. Microbiology and Infectious Disease
    2. Neuroscience

    A gut bacterial amyloid promotes α-synuclein aggregation and motor impairment in mice

    Timothy R Sampson et al.
    Production of an amyloid protein by bacteria within the gut microbiome can influence the pathophysiology of a mouse model of synucleinopathy.
    1. Cell Biology

    Stress-induced Cdk5 activity enhances cytoprotective basal autophagy in Drosophila melanogaster by phosphorylating acinus at serine437

    Nilay Nandi et al.
    Cdk5-mediated stabilization of Acinus in postmitotic neurons promotes autophagy and the removal of protein aggregates linked to neurodegeneration in Drosophila melanogaster.
    1. Neuroscience

    Depleting Trim28 in adult mice is well tolerated and reduces levels of α-synuclein and tau

    Maxime WC Rousseaux et al.
    Loss of a developmentally essential gene in adulthood is tolerated in mice, thus offering potential therapeutic options for Alzheimer's and Parkinson's disease.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Native α-synuclein induces clustering of synaptic-vesicle mimics via binding to phospholipids and synaptobrevin-2/VAMP2

    Jiajie Diao et al.
    Experiments on synthetic models of synaptic vesicles have shed new light on the role of the protein α-synuclein in the central nervous system.

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