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Europium-Doped Cerium Oxide Nanoparticles for Microglial Amyloid Beta Clearance and Homeostasis
Jatin Machhi1, Pravin Yeapuri2, Milica Markovic1
1Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, Nebraska 68198, United States.
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, 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.
Insights
Europium-doped cerium oxide nanoparticles (EuCeO2NPs) reduce Alzheimer's disease (AD) pathology by enhancing microglia's ability to clear amyloid beta (Aβ) plaques and reduce inflammation. This suggests potential for AD immunomodulation.
Area of Science:
- Neuroscience
- Nanotechnology
- Immunology
Background:
- Alzheimer's disease (AD) is a neurodegenerative disorder marked by amyloid beta (Aβ) plaques and neuroinflammation.
- Current treatments targeting Aβ plaque accumulation have uncertain effects on disease outcomes.
- Cerium oxide nanoparticles (CeO2NPs) show potential in reducing oxidative stress and inflammation in AD.
Purpose of the Study:
- To investigate the effects of novel europium-doped cerium oxide nanoparticles (EuCeO2NPs) on microglia neurotoxic responses in Alzheimer's disease models.
- To determine if EuCeO2NPs can restore cellular immune homeostasis in AD.
Main Methods:
- Synthesis of novel europium-doped cerium oxide nanoparticles (EuCeO2NPs).
- Exposure of microglia (BV2 cells) to Aβ1-42 peptides and EuCeO2NPs.
- Assessment of microglia inflammatory activities, phagocytic capacity, and Aβ degradation.
- Analysis of CD36 scavenger receptor expression and Aβ endolysosomal trafficking.
Main Results:
- EuCeO2NPs attenuated microglia inflammatory responses induced by Aβ1-42 exposure.
- Increased phagocytic and Aβ degradation activities of microglia were observed with EuCeO2NPs treatment.
- EuCeO2NPs treatment led to increased CD36 scavenger receptor expression and facilitated Aβ endolysosomal trafficking.
- Microglial inflammatory responses were abrogated by EuCeO2NPs.
Conclusions:
- EuCeO2NPs effectively modulate microglia responses in an AD context.
- These nanoparticles enhance the clearance of amyloid beta and reduce neuroinflammation.
- EuCeO2NPs show promise as a potential immunomodulatory therapeutic agent for Alzheimer's disease.
