Cerium oxide nanoparticles protect against Aß-induced mitochondrial fragmentation and neuronal cell death.
Cell Death Differ
; 21(10): 1622-32, 2014 Oct.
Article
em En
| MEDLINE
| ID: mdl-24902900
ABSTRACT
Evidence indicates that nitrosative stress and mitochondrial dysfunction participate in the pathogenesis of Alzheimer's disease (AD). Amyloid beta (Aß) 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 Ce(3+) and Ce(4+) 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 Aß-induced mitochondrial fragmentation, DRP1 S616 hyperphosphorylation and neuronal cell death.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cério
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Peptídeos beta-Amiloides
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Apoptose
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Mitofagia
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Mitocôndrias
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article