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

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 (CeO 2 ) reduces Aβ plaques, oxidative stress, inflammation, and AD signs and symptoms. In particular, CeO 2 nanoparticles (CeO 2 NPs) induce free-radical-scavenging and cell protective intracellular signaling. This can ameliorate the pathobiology of an ADaffected brain. To investigate whether CeO 2 NPs affect microglia neurotoxic responses, a novel formulation of europium-doped CeO 2 NPs (Eu-CeO 2 NPs) was synthesized. We then tested EuCeO 2 NPs for its ability to generate cellular immune homeostasis in AD models. EuCeO 2 NPs 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. EuCeO 2 NPs facilitated Aβ endolysosomal trafficking and abrogated microglial inflammatory responses. We posit that EuCeO 2 NPs may be developed as an AD immunomodulator.

Progress in bioactive surface coatings on biodegradable Mg alloys: A critical review towards clinical translation

“…In contrast, continued scratch growth was observed for conventionally coated samples by phosphate conversion method due to active corrosion. Nevertheless, Ce compounds are known for suppression of oxidative stress and free radical production, which otherwise, could promote several neurodegenerative diseases, such as Parkinson's disease, trauma, ischemic stroke, Alzheimer's disease (AD), and aging [ 96 ]. Recently, Ce based compounds are reported for promoting angiogenesis induction [ 97 ] and peroxidase mimicking activity [ 98 ] for breast cancer cell detection.…”

Recent Advances on Cerium Oxide‐Based Biomaterials: Toward the Next Generation of Intelligent Theranostics Platforms

“…[ 74 ] Researchers have found that CeO 2 has a potential therapeutic effect on these diseases. [ 75 ]…”

“…In particular, CeO 2 induces free radical scavenging and cytoprotective intracellular signaling, which could alleviate the pathobiology of AD‐affected brains. [ 75a ] Machhi et al. synthesized a potential agent of AD immunomodulator: europium‐doped CeO 2 (Eu‐CeO 2 NPs), which increases the phagocytosis and A β ‐degradation ability of cells, so the BV2 inflammatory activity of microglia after A β 1‐42 exposure is attenuated.…”

“…As the CD36 scavenger receptor expression increases, A β endolysosomal trafficking is promoted and microglial inflammatory response is abrogated, confirming the potential application of Eu‐CeO 2 in AD. [ 75a ]…”

Exploring the Physicochemical, Electroactive, and Biodelivery Properties of Metal Nanoparticles on Peripheral Nerve Regeneration

“…In general, the neuroprotective effect of CeO 2 NPs is superior to their other therapeutic capabilities based on their physicochemical properties as nanozymes in reducing radical agents. , Although the protective mechanisms of CeO 2 NPs and their optimum concentrations are still debatable, it has been confirmed that these NPs guide healing or regeneration activities by changing cell polarity from pro-inflammatory to anti-inflammatory phenotype. , In this regard, Ciofani et al using synthesized CeO 2 NPs with dimensions of 5–80 nm containing Ce 3+ and Ce 4+ were able to control the intracellular ROS in order to reduce the apoptosis by reducing Gss and Gpx1 gene expression and increase the neurite length from 55 to 85 μm. Also, they showed that the use of CeO 2 NPs with a concentration of 50 μg/mL increases the expression of β3 tubulin and neurofilaments-66 by 1.5 times .…”