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    1. Structural Biology and Molecular Biophysics

    Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer’s and Pick’s diseases

    Wenjuan Zhang, Benjamin Falcon ... Sjors HW Scheres
    Cryo-EM structures of heparin-induced tau filaments differ from those observed in neurodegenerative disease, illustrating their structural versatility, and prompting questions about the relevance of in vitro amyloid models.
    1. Neuroscience

    Clearance of beta-amyloid is facilitated by apolipoprotein E and circulating high-density lipoproteins in bioengineered human vessels

    Jerome Robert, Emily B Button ... Cheryl L Wellington
    Modelling beta-amyloid deposition in bioengineered human vessels represents a notable advance to further investigate the role of the vasculature in Alzheimer's disease.
    1. Structural Biology and Molecular Biophysics

    Structure-based discovery of fiber-binding compounds that reduce the cytotoxicity of amyloid beta

    Lin Jiang, Cong Liu ... David S Eisenberg
    By using structural methods to screen compounds for their ability to interact with amyloid beta, researchers have identified small molecules that stabilize amyloid fibers and reduce the toxic effect of smaller aggregates on cells.
    1. Biochemistry and Chemical Biology
    2. Neuroscience

    Alzheimer’s disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling

    Katarzyna Marta Zoltowska, Utpal Das ... Lucía Chávez-Gutiérrez
    A novel Aβ-driven inhibitory mechanism on γ-secretases, which leads to substrate accumulation and reduced release of products, contributes to neurotoxicity by impairing γ-secretase signaling and might operate in Alzheimer’s disease.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Atomic structures of fibrillar segments of hIAPP suggest tightly mated β-sheets are important for cytotoxicity

    Pascal Krotee, Jose A Rodriguez ... David S Eisenberg
    Atomic structures of hIAPP fibrillar segments, determined using the cryo electron microscopy method MicroED, reveal that strong, stable intermolecular interactions are important features of cytotoxic amyloid proteins.
    1. Neuroscience

    Fibrillar Aβ triggers microglial proteome alterations and dysfunction in Alzheimer mouse models

    Laura Sebastian Monasor, Stephan A Müller ... Sabina Tahirovic
    APPPS1 microglia express disease-associated proteomic signatures of Alzheimer's disease earlier, compared to the APP-KI, and these differences correlate with the levels of fibrillar Aβ and impaired microglial phagocytic function.
    1. Cell Biology
    2. Neuroscience

    Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer’s disease, restores synapse integrity and memory in a disease mouse model

    Nuria Martin Flores, Marina Podpolny ... Patricia C Salinas
    The Wnt antagonist DKK3 is a key regulator of excitatory and inhibitory synapses, and its downregulation in the hippocampus restores synaptic connectivity and memory in an Alzheimer's disease mouse model.
    1. Structural Biology and Molecular Biophysics

    Semen amyloids participate in spermatozoa selection and clearance

    Nadia R Roan, Nathallie Sandi-Monroy ... Warner C Greene
    Ex vivo characterization of the interaction of human sperm with semen factors reveals that semen amyloids, previously discovered due to their ability to enhance HIV infection, serve a physiological function by promoting disposal of the defective sperm.
    1. Structural Biology and Molecular Biophysics

    Pathologic polyglutamine aggregation begins with a self-poisoning polymer crystal

    Tej Kandola, Shriram Venkatesan ... Randal Halfmann
    The disease-associated aggregation of polyglutamine begins in a single molecule with a specific structure.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A molecular tweezer antagonizes seminal amyloids and HIV infection

    Edina Lump, Laura M Castellano ... Jan Münch
    CLR01 is a small molecule that could be an effective topical microbicide to eliminate HIV (and other enveloped viruses), and to antagonize host-encoded amyloid fibrils that promote HIV infection.