Curcumin-polydopamine nanoparticles alleviate ferroptosis by iron chelation and inhibition of oxidative stress damage.

Ferroptosis, characterized by elevated iron levels and lipid peroxidation (LPO), is a recently identified regulatory mechanism of cell death. Its substantial involvement in ischemic tissue injury, neurodegenerative disorders, and cancer positions ferroptosis inhibition as a promising strategy for managing these diverse diseases. In this study, we introduce curcumin-polydopamine nanoparticles (Cur-PDA NPs) as an innovative ferroptosis inhibitor. Cur-PDA NPs demonstrate remarkable efficacy in chelating both Fe2+ and Fe3+in vitro along with scavenging free radicals. Cur-PDA NPs were found to efficiently mitigate reactive oxygen species, reduce Fe2+ accumulation, suppress LPO, and rejuvenate mitochondrial function in PC12 cells. Thus, these NPs can act as potent therapeutic agents against ferroptosis, primarily via iron chelation and reduction of oxidative stress.

Alpha lipoic acid ameliorates motor deficits by inhibiting ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease. Ferroptosis shares several features with PD pathophysiology, and anti-ferroptosis molecules are neuroprotective in PD animal models. As an antioxidant and iron chelating agent, alpha lipoic acid (ALA) has a neuroprotective effect on PD; however, the influence of ALA on ferroptosis in PD remains unclear. This study aimed to determine the mechanism of ALA in regulating ferroptosis in PD models. Results showed that ALA could ameliorate motor deficits in PD models and regulate iron metabolism by upregulating ferroportin (FPN) and ferritin heavy chain 1 (FTH1) and downregulating iron importer divalent metal transporter 1 (DMT1). Moreover, ALA decreased the accumulation of reactive oxygen species (ROS) and lipid peroxidation, rescued mitochondrial damage, and prevented ferroptosis effectively by inhibiting the downregulation of glutathione peroxidase 4 (GPX4) and cysteine/glutamate transporter (xCT) in PD. Mechanistic study indicated that the activation of SIRT1/NRF2 pathway was involved in the upregulation effect of GPX4 and FTH1. Thus, ALA ameliorates motor deficits in PD models by regulating iron metabolism and mitigating ferroptosis through the SIRT1/NRF2 signaling pathway.

Self-assembled, hemin-functionalized peptide nanotubes: an innovative strategy for detecting glutathione and glucose molecules with peroxidase-like activity.

Accurately detecting dynamic changes in bioactive small molecules in real-time is very challenging. In this study, a hemin-based peptide assembly was rationally designed for the colorimetric detection of active small molecules. Hemin-functionalized peptide nanotubes were obtained through the direct incubation of hemin (hemin@PNTs) and peptide nanotubes (PNTs) or were coassembled with the heptapeptide Ac-KLVFFAL-NH2 via electrostatic, π-π stacking, and hydrophobic interactions (hemin-PNTs). This new substance is significant because it exhibits the benefits of both hemin and PNTs as well as some special qualities. First, hemin-PNTs exhibited higher intrinsic peroxidase-like activity, which, in the presence of H2O2, could catalyze the oxidation of the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to yield a typical blue solution after 10 min at 25 ℃. Second, hemin-PNTs showed significantly higher activity than that of hemin, PNTs alone, or hemin@PNTs. Hemin-PNTs with a 20.0% hemin content may cooperate to improve catalytic activity. The catalytic activity was dependent on the reaction temperature, pH, reaction time, and H2O2 concentration. The nature of the TMB-catalyzed reaction may arise from the production of hydroxyl radicals. Fluorescence analysis was used to demonstrate the catalytic mechanism. According to this investigation, a new highly selective and sensitive colorimetric technique for detecting glutathione (GSH), L-cysteine, and glucose was established. The strategy demonstrated excellent sensitivity for GSH in the range of 1 to 30 µM with a 0.51 µM detection limit. Importantly, this glucose detection technique, which employs glucose oxidase and hemin-PNTs, is simple and inexpensive, with a 0.1 µM to 1.0 mM linear range and a 15.2 µM detection limit. Because of their low cost and high catalytic activity, hemin-PNTs are an excellent choice for biocatalysts in a diverse range of potential applications, including applications in clinical diagnostics, environmental chemistry, and biotechnology.