TY - JOUR
T1 - Exposure to CuO nanoparticles mediates NFκB activation and enhances amyloid precursor protein expression
AU - Mou, Xiaoyang
AU - Pilozzi, Alexander
AU - Tailor, Breeya
AU - Yi, Jing
AU - Cahill, Catherine
AU - Rogers, Jack
AU - Huang, Xudong
N1 - Funding Information:
Funding: This work is partially funded by a grant from the NIH grant number R01AG056614 (to X.H.).
Publisher Copyright:
© 2020 by the authors.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Amyloid precursor protein (APP) is directly related to Aβ amyloidosis-a hallmark of Alzheimer's disease (AD). However, the impact of environmental factors upon APP biology and Aβ amyloid pathology have not been well studied. The increased use of nanoparticles (NPs) or engineered nanomaterials (ENMs) has led to a growing body of evidence suggesting that exposure to metal/metal oxide NPs, such as Fe2O3, CuO, and ZnO, may contribute to the pathophysiology of neurodegenerative diseases such as AD through neuroinflammation. Our previous studies indicated that exposure to CuO nanoparticles (CuONPs) induce potent in vitro neurotoxicity. Herein, we investigated the effects on APP expression in neuronal cells exposed to different metal oxide NPs. We found a low dose of CuONPs effectively activated the NFκB signaling pathway and increased APP expression. Moreover, the inhibition of p65 expression using siRNA abolished CuONP-mediated APP expression, suggesting that NFκB-regulated APP expression in response to CuONP exposure may be associated with AD pathology.
AB - Amyloid precursor protein (APP) is directly related to Aβ amyloidosis-a hallmark of Alzheimer's disease (AD). However, the impact of environmental factors upon APP biology and Aβ amyloid pathology have not been well studied. The increased use of nanoparticles (NPs) or engineered nanomaterials (ENMs) has led to a growing body of evidence suggesting that exposure to metal/metal oxide NPs, such as Fe2O3, CuO, and ZnO, may contribute to the pathophysiology of neurodegenerative diseases such as AD through neuroinflammation. Our previous studies indicated that exposure to CuO nanoparticles (CuONPs) induce potent in vitro neurotoxicity. Herein, we investigated the effects on APP expression in neuronal cells exposed to different metal oxide NPs. We found a low dose of CuONPs effectively activated the NFκB signaling pathway and increased APP expression. Moreover, the inhibition of p65 expression using siRNA abolished CuONP-mediated APP expression, suggesting that NFκB-regulated APP expression in response to CuONP exposure may be associated with AD pathology.
UR - http://www.scopus.com/inward/record.url?scp=85083734264&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083734264&partnerID=8YFLogxK
U2 - 10.3390/biomedicines8030045
DO - 10.3390/biomedicines8030045
M3 - Article
AN - SCOPUS:85083734264
SN - 2227-9059
VL - 8
JO - Biomedicines
JF - Biomedicines
IS - 3
M1 - 45
ER -