Membrane-induced tau amyloid fibrils

Mammeri, Nadia El; Gampp, Olivia; Duan, Pu; Hong, Mei

doi:10.1038/s42003-023-04847-6

Cited by 11 publications

(7 citation statements)

References 90 publications

(104 reference statements)

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“…When OptoTau was expressed, the confinement length of EGFR diffusion extended regardless of the tau aggregation. Previous studies suggested a direct interaction of both soluble and filamentous tau protein with the plasma membrane especially lipid raft [28,29]. The confinement region for the slow-mobile state was indicated to correspond to a membrane subdomain [1], and the size of which is similar to a lipid raft.…”

Section: Effect Of Tau Aggregation On Receptor Mobilitymentioning

confidence: 83%

Application of single-molecule analysis to singularity phenomenon of cells

Hiroshima,

Bannai,

Matsumoto

et al. 2024

BIOPHYSICS

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Single-molecule imaging in living cells is an effective tool for elucidating the mechanisms of cellular phenomena at the molecular level. However, the analysis was not designed for throughput and requires high expertise, preventing it from reaching large scale, which is necessary when searching for rare cells that induce singularity phenomena. To overcome this limitation, we have automated the imaging procedures by combining our own focusing device, artificial intelligence, and robotics. The apparatus, called automated in-cell single-molecule imaging system (AiSIS), achieves a throughput that is a hundred-fold higher than conventional manual imaging operations, enabling the analysis of molecular events by individual cells across a large population. Here, using AiSIS, we demonstrate the single-molecule imaging of molecular behaviors and reactions related to tau protein aggregation, which is considered a singularity phenomenon in neurological disorders. Changes in the dynamics and kinetics of molecular events were observed inside and on the basal membrane of cells after the induction of aggregation. Additionally, to detect rare cells based on the molecular behavior, we developed a method to identify the state of individual cells defined by the quantitative distribution of molecular mobility and clustering. Using this method, cellular variations in receptor behavior were shown to decrease following ligand stimulation. This cell state analysis based on large-scale single-molecule imaging by AiSIS will advance the study of molecular mechanisms causing singularity phenomena.

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Section: Effect Of Tau Aggregation On Receptor Mobilitymentioning

confidence: 83%

Application of single-molecule analysis to singularity phenomenon of cells

Hiroshima,

Bannai,

Matsumoto

et al. 2024

BIOPHYSICS

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“…Furthermore, previous studies have established that tau proteins interact with membrane lipids, crucial in AD and other neurodegenerative disorders. 50 Therefore, the observed expression of AT8 due to SARS-CoV-2 infection suggests a potential link between SARS-CoV-2 infection and AD. In this study, we have found reasonable evidence for increased tau pathology during SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 95%

Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

Choi,

Gadhave,

Villano

et al. 2024

Journal of Medical Virology

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Although the COVID‐19 pandemic has officially ended, the persistent challenge of long‐COVID or post‐acute COVID sequelae (PASC) continues to impact societies globally, highlighting the urgent need for ongoing research into its mechanisms and therapeutic approaches. Our team has recently developed a novel humanized ACE2 mouse model (hACE2ki) designed explicitly for long‐COVID/PASC research. This model exhibits human ACE2 expression in tissue and cell‐specific patterns akin to mouse Ace2. When we exposed young adult hACE2ki mice (6 weeks old) to various SARS‐CoV‐2 lineages, including WA, Delta, and Omicron, at a dose of 5 × 105 PFU/mouse via nasal instillation, the mice demonstrated distinctive phenotypes characterized by differences in viral load in the lung, trachea, and nasal turbinate, weight loss, and changes in pro‐inflammatory cytokines and immune cell profiles in bronchoalveolar lavage fluid. Notably, no mortality was observed in this age group. Further, to assess the model's relevance for long‐COVID studies, we investigated tau protein pathologies, which are linked to Alzheimer's disease, in the brains of these mice post SARS‐CoV‐2 infection. Our findings revealed the accumulation and longitudinal propagation of tau, confirming the potential of our hACE2ki mouse model for preclinical studies of long‐COVID.

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“…Within intrinsically disordered proteins, lipid-binding occurs in more structured regions, such as the relatively more ordered repeat region in tau where its prion properties reside 62 . Indeed, using solid-state NMR and transmission electron microscopy, a tau construct encoding the microtubule-binding repeats and a proline-rich domain was reconstituted into cholesterol-containing phospholipid membranes in a transition from a random coil to a β-sheet conformation over weeks 63 . Cellular aggregates displayed colocalization with VCP and SQSTM1, proteins essential for aggresome formation and selective autophagy 47–49,53,64 .…”

Section: Discussionmentioning

confidence: 99%

Precision Proteoform Design for 4R Tau Isoform Selective Templated Aggregation

Longhini,

DuBose,

Lobo

et al. 2023

Preprint

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Prion-like spread of disease-specific tau conformers is a hallmark of all tauopathies. We used a 19-residue probe peptide spanning the R2/R3 splice junction of tau to induce aggregation specifically of 4R, but not 3R tau. The aggregates can propagate as isoform-specific seeds over multiple generations, have a high β-sheet content, a lipid signal, and resemble the PSP cryo-EM fold. A simulation of peptide free energy landscapes pinpointed the features of the hairpin structure uniquely found in the cryo-EM structures of pure 4R tauopathies and captured in the peptide. These molecular dynamic simulations were experimentally validated by the S305K substitution in 4R tau, corresponding to the position found in 3R tau. This single amino acid substitution prevented tau aggregates induced by the prion-like probe peptide. The tau aggregates were dynamic and displayed growth, stability, and shrinking over time. These results could serve as the basis for tau isoform-specific therapeutic interventions.

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Membrane-induced tau amyloid fibrils

Cited by 11 publications

References 90 publications

Application of single-molecule analysis to singularity phenomenon of cells

Application of single-molecule analysis to singularity phenomenon of cells

Generation and characterization of a humanized ACE2 mouse model to study long‐term impacts of SARS‐CoV‐2 infection

Precision Proteoform Design for 4R Tau Isoform Selective Templated Aggregation

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