Europium-doped cerium oxide nanoparticles for microglial Aβ clearance and homeostasis

Authors

Jatin Machhi, University of Nebraska Medical CenterFollow
Pravin Yeapuri, Xi’an Jiaotong University Health Science Center
Milica Markovic, University of Nebraska Medical Center
Milankumar Patel, University of Nebraska Medical Center
Wenhui Yan, Xi’an Jiaotong University Health Science Center
Yaman Lu, University of Nebraska Medical CenterFollow
Jacob D. Cohen, University of Nebraska Medical CenterFollow
Mahmudul Hasan, University of Nebraska Medical CenterFollow
Mai Mohamed Abdelmoaty, University of Nebraska Medical Center
You Zhou, University of Nebraska-Lincoln
Huangui Xiong, University of Nebraska Medical CenterFollow
Xinglong Wang, University of Nebraska Medical CenterFollow
R. Lee Mosley, University of Nebraska Medical CenterFollow
Howard E. Gendelman, University of Nebraska Medical CenterFollow
Bhavesh D. Kevadiya, University of Nebraska Medical CenterFollow

Document Type

Article

Date of this Version

4-20-2022

Citation

Published in final edited form as: ACS Chem Neurosci. 2022 April 20; 13(8): 1232–1244.

doi:10.1021/acschemneuro.1c00847.

Author manuscript; available in PMC 2022 June 24.

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder. Pathologically, it is characterized by the deposition of amyloid beta (Aβ) plaques and presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation was achieved how it affects disease outcomes remains uncertain. Cerium oxide (CeO₂) reduces Aβ plaques, oxidative stress, inflammation, and Alzheimer’s disease (AD) signs and symptoms. Specifically, CeO₂ nanoparticles (CeO₂NPs) induces free radical scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. In order to investigate, CeO₂NPs affects for microglia neurotoxic responses a novel formulation of europium doped CeO₂NPs (EuCeO₂NPs) was synthesized. We then tested EuCeO₂NPs for its’ abilities to generate cellular immune homeostasis in AD models. EuCeO₂NPs attenuated microglia BV2 inflammatory activities after Aβ_1–42 exposure by increasing the cells’ phagocytic and Aβ degradation activities. These were associated with increases in the expression of the CD36 scavenger receptor. EuCeO₂NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO₂NPs may be developed as an AD immunomodulator.