Title

Cerium oxide nanoparticles protect against A beta-induced mitochondrial fragmentation and neuronal cell death

Authors

Authors

J. M. Dowding; W. Song; K. Bossy; A. Karakoti; A. Kumar; A. Kim; B. Bossy; S. Seal; M. H. Ellisman; G. Perkins; W. T. Self;E. Bossy-Wetzel

Comments

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Abbreviated Journal Title

Cell Death Differ.

Keywords

ALZHEIMERS-DISEASE; NITRIC-OXIDE; OXIDATIVE STRESS; AMYLOID-BETA; S-NITROSYLATION; MOUSE MODEL; DRP1; SUPEROXIDE; FISSION; DAMAGE; Biochemistry & Molecular Biology; Cell Biology

Abstract

Evidence indicates that nitrosative stress and mitochondrial dysfunction participate in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (A beta) 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 A beta-induced mitochondrial fragmentation, DRP1 S616 hyperphosphorylation and neuronal cell death.

Journal Title

Cell Death and Differentiation

Volume

21

Issue/Number

10

Publication Date

1-1-2014

Document Type

Article

Language

English

First Page

1622

Last Page

1632

WOS Identifier

WOS:000343296400012

ISSN

1350-9047

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