RESUMO
Amyloid ß-peptide (Aß) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer's disease (AD). Aß oligomer (Aßo) exerts its neurotoxic effects by inducing oxidative stress and lesions by adhering to cellular membranes. Though several antidepressants have been investigated as neuroprotective agents in AD, a detailed comparison of their neuroprotection against Aßo-induced neurotoxicity is lacking. Here, we aimed to elucidate the neuroprotective effects of clinically prescribed selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants at the cellular level and establish the underlying mechanisms for their potential clinical applications. Therefore, we compared the neuroprotective effects of three antidepressants, fluoxetine (Flx), duloxetine (Dlx), and mirtazapine (Mir), by their ability to prevent oxidative stress-induced cell damage, using SH-SY5Y cells, by evaluating cell viability, generation of reactive oxygen species (ROS) and mitochondrial ROS, and peroxidation of cell membrane phospholipids. These antidepressants exhibited potent antioxidant activity (Dlx > Mir > Flx) and improved cell viability. Furthermore, pretreatment with a 5-hydroxytryptamine 1A (5-HT1A) antagonist suppressed their effects, suggesting that the 5-HT1A receptor is involved in the antioxidant mechanism of the antidepressants' neuroprotection. These findings suggest the beneficial effects of antidepressant treatment in AD through the prevention of Aß-induced oxidative stress.
RESUMO
Despite significant advances in atomically precise Au clusters with chirality, Ag clusters with the relevant features are still less explored. In this study, we report successful synthesis of chiral Ag29 clusters protected by water-soluble monothiol in one pot, which is carried out by reducing Ag ions in the presence of N-acetyl-(S)-penicillamine (S-NAP) and triphenylphosphine (TPP) at 10 °C, yielding the Ag29(S-NAP)24 cluster. The obtained cluster is isolable as a solid-state powder. Optical absorption of Ag29(S-NAP)24 is almost identical with that of Ag29(R-DHLA)12, where DHLA denotes α-dihydrolipoic acid, and magnetic circular dichroism (MCD) results support the similarity of their electronic structures. The anisotropy factor of Ag29(S-NAP)24 is comparable to or larger than that of Ag29(R-DHLA)12, suggesting that the surface shell structure of Ag29(S-NAP)24 is inherently chiral, as has been observed for Ag29(R-DHLA)12. Then the use of enantiopure NAP would preferentially lead to a one-handed atomic arrangement in the clusters.
