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 (Ab) 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 þ and Ce 4 þ 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 Ab-induced mitochondrial fragmentation, DRP1 S616 hyperphosphorylation and neuronal cell death.

Cerium oxide nanoparticles promote neurogenesis and abrogate hypoxia-induced memory impairment through AMPK–PKC–CBP signaling cascade

“…Similarly, CNPs with PEG as well as citrate/EDTA coatings have been used for free radical scavenging and specific targeting to amyloid beta (Aβ) aggregates. 27 In the present study, we extend the usage of ζ ζ Figure 7 evaluation of key molecular targets of Peg-cNPs using immunoblotting. Notes: Immunoblots show changes in expression or phosphorylation of neurogenic and apoptotic markers in the rat brain homogenates.…”

“…Our present study also suggests that PEG-CNPs with ,5 nm size efficiently cross the BBB and localize in the brain. 27,29,42 PEG-coated CNPs exhibit excellent stability and disparity in physiological solutions, as well as efficiently quench noxious free radicals and peroxides mimicking superoxide dismutase activity, as compared to bare CNPs. 42,43 Hence, we evaluated the in vivo antioxidant activities and the level of oxidative modification of proteins after 10 days of hypobaric hypoxia exposure.…”

“…The neuroprotective efficacies of nanoceria have been studied in adult rat spinal cord neurons, 23 brain slice model of ischemia, 24 animal models of ischemic stroke, 25 multiple sclerosis, 26 and Parkinson's disease. 27 These studies have reported efficient neuroprotection activities of nanoceria, primarily by reducing nitrosative stress. 24,27,28 In this study, we evaluated the neuroprotective efficacy as well as cognition-promoting activities of CNP nanoparticles during chronic hypobaric hypoxia.…”

“…27 These studies have reported efficient neuroprotection activities of nanoceria, primarily by reducing nitrosative stress. 24,27,28 In this study, we evaluated the neuroprotective efficacy as well as cognition-promoting activities of CNP nanoparticles during chronic hypobaric hypoxia. Using polyethylene glycol (PEG) coating, we ensured brain delivery and penetration of CNPs within the brain tissue, 25,[29][30][31] which was confirmed by imaging studies.…”

Functional Recovery of Contused Spinal Cord in Rat with the Injection of Optimal‐Dosed Cerium Oxide Nanoparticles

“…Thus they have shown interesting biological properties, including ROS scavenging 6. The cellular responses to CONPs vary depending on the cell type.…”