Title

Cerium Oxide Nanoparticles Protect Against Aβ-Induced Mitochondrial Fragmentation And Neuronal Cell Death

Abstract

Evidence indicates that nitrosative stress and mitochondrial dysfunction participate in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (Aβ) and peroxynitrite induce mitochondrial fragmentation and neuronal cell death by abnormal activation of dynamin-related protein 1 (DRP1), a large GTPase that regulates mitochondrial fission. The exact mechanisms of mitochondrial fragmentation and DRP1 overactivation in AD remain unknown; however, DRP1 serine 616 (S616) phosphorylation is likely involved. Although it is clear that nitrosative stress caused by peroxynitrite has a role in AD, effective antioxidant therapies are lacking. Cerium oxide nanoparticles, or nanoceria, switch between their Ce3+ and Ce4+ states and are able to scavenge superoxide anions, hydrogen peroxide and peroxynitrite. Therefore, nanoceria might protect against neurodegeneration. Here we report that nanoceria are internalized by neurons and accumulate at the mitochondrial outer membrane and plasma membrane. Furthermore, nanoceria reduce levels of reactive nitrogen species and protein tyrosine nitration in neurons exposed to peroxynitrite. Importantly, nanoceria reduce endogenous peroxynitrite and Aβ-induced mitochondrial fragmentation, DRP1 S616 hyperphosphorylation and neuronal cell death.

Publication Date

10-1-2014

Publication Title

Cell Death and Differentiation

Volume

21

Issue

10

Number of Pages

1622-1632

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1038/cdd.2014.72

Socpus ID

84928997316 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84928997316

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