Bisdemethoxycurcumin (BDC)-Loaded H-Ferritin-Nanocages Mediate the Regulation of Inflammation in Alzheimer’s Disease Patients

Autor: Stella Gagliardi, Marta Truffi, Veronica Tinelli, Maria Garofalo, Cecilia Pandini, Matteo Cotta Ramusino, Giulia Perini, Alfredo Costa, Sara Negri, Serena Mazzucchelli, Arianna Bonizzi, Leopoldo Sitia, Maria Busacca, Marta Sevieri, Michela Mocchi, Alessandra Ricciardi, Davide Prosperi, Fabio Corsi, Cristina Cereda, Carlo Morasso
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 23, Iss 16, p 9237 (2022)
Druh dokumentu: article
ISSN: 1422-0067
1661-6596
DOI: 10.3390/ijms23169237
Popis: Background: Bisdemethoxycurcumin (BDC) might be an inflammation inhibitor in Alzheimer’s Disease (AD). However, BDC is almost insoluble in water, poorly absorbed by the organism, and degrades rapidly. We thus developed a new nanoformulation of BDC based on H-Ferritin nanocages (BDC-HFn). Methods: We tested the BDC-HFn solubility, stability, and ability to cross a blood–brain barrier (BBB) model. We tested the effect of BDC-HFn on AD and control (CTR) PBMCs to evaluate the transcriptomic profile by RNA-seq. Results: We developed a nanoformulation with a diameter of 12 nm to improve the solubility and stability. The comparison of the transcriptomics analyses between AD patients before and after BDC-HFn treatment showed a major number of DEG (2517). The pathway analysis showed that chemokines and macrophages activation differed between AD patients and controls after BDC-HFn treatment. BDC-HFn binds endothelial cells from the cerebral cortex and crosses through a BBB in vitro model. Conclusions: Our data showed how BDC-Hfn could improve the stability of BDC. Significant differences in genes associated with inflammation between the same patients before and after BDC-Hfn treatment have been found. Inflammatory genes that are upregulated between AD and CTR after BDC-HFn treatment are converted and downregulated, suggesting a possible therapeutic approach.
Databáze: Directory of Open Access Journals
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