Europium-Doped Cerium Oxide Nanoparticles for Microglial Amyloid Beta Clearance and Homeostasis

Jatin MacHhi, Pravin Yeapuri, Milica Markovic, Milankumar Patel, Wenhui Yan, Yaman Lu, Jacob D. Cohen, Mahmudul Hasan, Mai Mohamed Abdelmoaty, You Zhou, Huangui Xiong, Xinglong Wang, R. Lee Mosley, Howard E. Gendelman, Bhavesh D. Kevadiya

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Pathologically, the disease is characterized by the deposition of amyloid beta (Aβ) plaques and the presence of neurofibrillary tangles. These drive microglia neuroinflammation and consequent neurodegeneration. While the means to affect Aβ plaque accumulation pharmacologically was achieved, how it affects disease outcomes remains uncertain. Cerium oxide (CeO2) reduces Aβ plaques, oxidative stress, inflammation, and AD signs and symptoms. In particular, CeO2nanoparticles (CeO2NPs) induce free-radical-scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an AD-affected brain. To investigate whether CeO2NPs affect microglia neurotoxic responses, a novel formulation of europium-doped CeO2NPs (EuCeO2NPs) was synthesized. We then tested EuCeO2NPs for its ability to generate cellular immune homeostasis in AD models. EuCeO2NPs attenuated microglia BV2 inflammatory activities after Aβ1-42exposure 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.

Original languageEnglish (US)
Pages (from-to)1232-1244
Number of pages13
JournalACS Chemical Neuroscience
Volume13
Issue number8
DOIs
StatePublished - Apr 20 2022

Keywords

  • Alzheimer's disease (AD)
  • BV2 cells and immune modulation
  • amyloid beta (Aβ)
  • cerium oxide
  • europium-doped cerium oxide nanoparticles (EuCeONPs)
  • microglia

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Cognitive Neuroscience
  • Cell Biology

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