Objective: Abeta leads to neurodegeneration and memory impairment via critical signal transduction processes, both at central and peripheral level. Studying the oligomeric-Abeta toxicity could helpful to clarify these phenomena, and to develop therapeutic and effective prevention technologies. Nanoparticles (NPs) biocompatibility and their ability to modulate Abeta toxicity were investigated in primary cultures from human fibroblasts. Methods: Control fibroblasts were incubated with Abeta oligomers and NP, functionalized or not with a ApoE monomer (mApo). By MTT assay we evaluate energetic metabolism and cell viability. Western Blot and p-Elisa were performed to evidence any modulation of MAPK and Tau hyperphosphorylation. By uptake studies and confocal images, we investigated the involvement of NPs in modulating the Abeta-induced excitotoxicity and their interaction with oligomers. By commercial kit, malondialdehyde levels were tested. Results: NPs do not affect cell viability, they prevent the Abeta-induced deficit of mitochondrial activity (p<0.001) and MAPK phosphorylation (p<0.001). mApo cross cell membrane, bind oligomers and modulate glutamate uptake in a dose dependent manner (p<0.01); they counteract the increase of Abeta–induced lipid peroxidation (p<0.002) and Tau-hyperphosphorylation (p<0.0001). Conclusion: These results suggest that NPs could represent a useful tool to antagonize Abeta oligomers toxicity, counteracting the cellular stress, protein epigenetic regulation and glutamate cytotoxicity. The modulations of MAPK pathways, altered by Abeta oligomers, might clarify any molecular mechanisms that mirror those involved in the early AD phases, and NPs may be useful to study new potential therapeutic strategies.
Zoia, C., Conti, E., Cereda, D., Rodriguez-Menendez, V., Andreoni, S., Gregori, M., et al. (2016). THE TOXICITY OF AMYLOID-BETA OLIGOMERS AND TAU HYPERPHOSPHORYLATION ARE PREVENTED FROM LIPID-BASED NANOPARTICLES IN HUMAN PRIMARY FIBOBLASTS. JOURNAL OF ALZHEIMER'S DISEASE.
|Citazione:||Zoia, C., Conti, E., Cereda, D., Rodriguez-Menendez, V., Andreoni, S., Gregori, M., et al. (2016). THE TOXICITY OF AMYLOID-BETA OLIGOMERS AND TAU HYPERPHOSPHORYLATION ARE PREVENTED FROM LIPID-BASED NANOPARTICLES IN HUMAN PRIMARY FIBOBLASTS. JOURNAL OF ALZHEIMER'S DISEASE.|
|Tipo:||Abstract in rivista|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||No|
|Titolo:||THE TOXICITY OF AMYLOID-BETA OLIGOMERS AND TAU HYPERPHOSPHORYLATION ARE PREVENTED FROM LIPID-BASED NANOPARTICLES IN HUMAN PRIMARY FIBOBLASTS|
|Autori:||Zoia, C; Conti, E; Cereda, D; Rodriguez-Menendez, V; Andreoni, S; Gregori, M; Sesana, M; Masserini, M; Tremolizzo, L; Ferrarese, C|
ZOIA, CHIARA PAOLA (Primo)
CONTI, ELISA (Secondo)
SESANA, MARIA SILVIA (Corresponding)
TREMOLIZZO, LUCIO (Penultimo)
FERRARESE, CARLO (Ultimo)
|Data di pubblicazione:||2016|
|Rivista:||JOURNAL OF ALZHEIMER'S DISEASE|
|Appare nelle tipologie:||01 - Articolo su rivista|