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Abstract
Oxidative stress and dysfunctional mitochondria are among the earliest events in AD, triggering neurodegeneration. The use of natural antioxidants could be a neuroprotective strategy for blocking cell death. Here, the antioxidant action of ferulic acid (FA) on different paths leading to degeneration of recombinant β-amyloid peptide (rAβ42) treated cells was investigated. Further, to improve its delivery, a novel drug delivery system (DDS) was used. Solid lipid nanoparticles (SLNs), empty or containing ferulic acid (FA-SNL), were developed as DDS. The resulting particles had small colloidal size and highly negative surface charge in water. Using neuroblastoma cells and rAβ42 oligomers, it was demonstrated that free and SLNs-loaded FA recover cell viability. FA treatment, in particular if loaded into SLNs, decreased ROS generation, restored mitochondrial membrane potential (Δψm) and reduced cytochrome c release and intrinsic pathway apoptosis activation. Further, FA modulated the expression of Peroxiredoxin, an anti-oxidative protein, and attenuated phosphorylation of ERK1/2 activated by Aβ oligomers.
| Abbreviations | ||
| Aβ | = | amyloid-beta peptide |
| AD | = | Alzheimer's disease |
| BBB | = | blood–brain barrier |
| CNS | = | central nervous system |
| DCF | = | 2′,7′-dichlorofluorescein |
| DDS | = | drug delivery systems |
| FA | = | ferulic acid |
| MPS | = | mononuclear phagocyte system |
| NDGA | = | nordihydroguaiaretic acid |
| PCS | = | photon correlation spectroscopy |
| PDI | = | polydispersity index |
| ROS | = | reactive oxygen species |
| rAβ42 | = | recombinant amyloid-beta peptide 42 |
| SLNs | = | solid lipid nanoparticles |
| Abbreviations | ||
| Aβ | = | amyloid-beta peptide |
| AD | = | Alzheimer's disease |
| BBB | = | blood–brain barrier |
| CNS | = | central nervous system |
| DCF | = | 2′,7′-dichlorofluorescein |
| DDS | = | drug delivery systems |
| FA | = | ferulic acid |
| MPS | = | mononuclear phagocyte system |
| NDGA | = | nordihydroguaiaretic acid |
| PCS | = | photon correlation spectroscopy |
| PDI | = | polydispersity index |
| ROS | = | reactive oxygen species |
| rAβ42 | = | recombinant amyloid-beta peptide 42 |
| SLNs | = | solid lipid nanoparticles |