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

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, CeO2 nanoparticles (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 Aβ1-42 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.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

ACS chemical neuroscience - 13(2022), 8 vom: 20. Apr., Seite 1232-1244

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

30K4522N6T
444W947O8O
619G5K328Y
Alzheimer’s disease (AD)
Amyloid beta (Aβ)
Amyloid beta-Peptides
BV2 cells and immune modulation
Ceric oxide
Cerium
Cerium oxide
Europium
Europium-doped cerium oxide nanoparticles (EuCeO2NPs)
Journal Article
Microglia
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Anmerkungen:

Date Completed 21.04.2022

Date Revised 12.04.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1021/acschemneuro.1c00847

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338427708