Curcumin tautomerization in the mechanism of pentameric amyloid- β42 oligomers disassembly

Matsui, Atsuya; Bellier, Jean-Pierre; Hayashi, Daiki; Ishibe, Takafumi; Nakamura, Yoshiaki; Taguchi, Hiroyasu; Naruse, Nobuyasu; Mera, Yutaka

doi:10.1016/j.bbrc.2023.04.076

Cited by 2 publications

(1 citation statement)

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“…Binding assays were performed after removing unbound IgG and blocking the reactive site on the sensor. Different concentrations of Aβ peptide of residues 2-42 prepared in 100 mM PBS as previously described 10 or purified fibrinogen from human blood prepared in 100 mM PBS + 0.5% BSA were injected, and data were collected.…”

Section: Surface Plasmon Resonance (Spr)mentioning

confidence: 99%

Identification of Fibrinogen as a Plasma Protein Binding Partner for Lecanemab Biosimilar IgG: Implications for Alzheimer’s Disease Therapy

Bellier,

Román Viera,

Christiano

et al. 2024

Preprint

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Objective: Recombinant monoclonal therapeutic antibodies like lecanemab, which target amyloid beta in Alzheimer's disease, offer a promising approach for modifying the disease progression. Due to its relatively short half-life, Lecanemab, administered as a bi-monthly infusion (typically 10mg/kg) has a relatively brief half-life. Interaction with abundant plasma proteins binder in the bloodstream can affect pharmacokinetics of drugs, including their half-life. In this study we investigated potential plasma protein binding interaction to lecanemab using lecanemab biosimilar. Methods: Lecanemab biosimilar used in this study was based on publicly available sequences. ELISA and Western blotting were used to assess lecanemab biosimilar immunoreactivity in the fractions human plasma sample obtained through size exclusion chromatography. The binding of lecanemab biosimilar to candidate binders was confirmed by Western blotting, ELISA, and surface plasmon resonance analysis. Results: Using a combination of equilibrium dialysis, ELISA, and Western blotting in human plasma, we first describe the presence of likely plasma protein binding partner to lecanemab biosimilar, and then identify fibrinogen as one of them. Utilizing surface plasmon resonance, we confirmed that lecanemab biosimilar does bind to fibrinogen, although with lower affinity than to monomeric amyloid beta. Conclusion: In the context of lecanemab therapy, these results imply that fibrinogen levels could impact the levels of free antibodies in the bloodstream and that fibrinogen might serve as a reservoir for lecanemab. More broadly, these results indicate that plasma protein binding may be an important consideration when clinically utilizing therapeutic antibodies in neurodegenerative disease.

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Section: Surface Plasmon Resonance (Spr)mentioning

confidence: 99%