The generation of excessive mitochondrial reactive oxygen species (mtROS) is associated with glutamate-stimulated neurotoxicity and pathogenesis of Alzheimer's disease (AD). Impaired mitochondrial function is accompanied with oxidative stress that is a significant contributor to initiate autophagy, but the underlying mechanisms are not fully understood. The present study aimed to investigate the neuroprotective effects of Mito-Tempo on glutamate-induced neuroblastoma SH-SY5Y cell toxicity. SH-SY5Y cells were treated with 100 μM glutamate in the presence or absence of 50 and 100 μM Mito-Tempo for 24 h. Changes in cell viability were measured by MTT assay. Cytotoxicity and intracellular ROS accumulation were also evaluated using lactate dehydrogenase (LDH) activity assay and 2,7-dichlorofluorescein diacetate (DCFDA) Reactive Oxygen Species Assay kit, respectively. Mitochondrial membrane potential was analyzed by tetraethylbenzimidazoly-lcarbocyanine iodide (JC-1) staining. Expression of PI3K/AKT/mTOR pathway and autophagy markers, including LC3 (LC3-I/-II) and p62 (SQSTM1) were performed using Western blot analysis. Our results demonstrated that glutamate-exposed cells significantly increased cellular oxidative stress by enhancing ROS production. Glutamate treatment also increased LDH release follows the loss of mitochondrial membrane potential, caused cell viability loss. Treatment with Mito-Tempo not only attenuated the generation of ROS and improved mitochondrial membrane potential but also reduced the neurotoxicity of glutamate in a concentration-dependent manner, which leads to increased cell viability and decreased LDH release. Mito-Tempo has a greater protective effect by enhancing superoxide dismutase (SOD) activity and PI3K/AKT/mTOR phosphorylation. Moreover, Mito-Tempo treatment altered the autophagy process resulting in the decline in the ratio of the autophagy markers LC3-I/-II and p62 (SQSTM1). We propose that Mito-Tempo can improve neuronal properties against glutamate cytotoxicity through its direct free radical scavenging activity and inhibit excessive autophagy signaling pathway, therefore, allow for further studies to investigate the therapeutic potentials of Mito-Tempo in animal disease models and human.

Increasing evidence highlights that excessive iron accumulation in the brain plays a vital role in neuronal senescence and is implicated in the pathogenesis of age-related neurodegenerative diseases, including Alzheimers disease (AD) and Parkinsons disease (PD). Therefore, the chemical compounds that eliminate an iron overload may provide better protection against oxidative stress conditions that cause the accumulation of senescent cells during brain aging. Ebselen has been identified as a strongly useful compound in the research on redox biology mechanisms. We hypothesized that ebselen could alleviate an iron overload-induced oxidative stress and consequently reverses the senescence-like phenotypes in the neuronal cells. In the present study, SH-SY5Y cells were treated with ferric ammonium citrate (FAC) before ebselen, and the evaluation of the cellular iron homeostasis, the indicators of oxidative stress, and the onset of senescence phenotypes and mechanisms were carried out accordingly. Our findings showed that ebselen ameliorated the FAC-mediated iron overload by decreasing the expression of divalent metal transporter 1 (DMT1) and ferritin light chain (FT-L) proteins. In contrast, it increased the expression of ferroportin 1 (FPN1) protein and its correlation led to a decrease in the expression of the cytosolic labile iron pool (LIP). Furthermore, ebselen significantly reduced reactive oxygen species (ROS) and rescued the mitochondrial membrane potential (ΔΨm). Notably, ebselen restored the biomarkers of cellular senescence by reducing the number of senescence-associated β-galactosidase (SA-β-gal) positive cells and senescence-associated secretory phenotypes (SASP). This also suppressed the expression of p53 protein targeting DNA damage response (DDR)/p21 cyclin-dependent kinase (CDK) inhibitor through a mTORC1 signaling pathway. Potentially, ebselen could be a therapeutic agent for treating brain aging and AD by mitigating iron accumulation and restoring senescence in SH-SY5Y cells.

Pyrokinins (PKs) are neuropeptides that have been found to regulate a variety of physiological activities including reproduction in various insect and crustacean species. However, the reproductive roles of PKs in the giant freshwater prawn, Macrobrachium rosenbergii, have not yet been investigated. In this study, we identified the MroPK gene from next-generation sequence resources, which encodes a MroPK precursor that shares a high degree of conservation with the C-terminal sequence of FxPRLamide in other arthropods. MroPK is expressed within most tissues, except the hepatopancreas, stomach and gill. Within developing ovarian tissue, MroPK expression was found to be significantly higher during the early stages (stages 1–2) compared with the late stages (stages 3–4), and could be localized to the oogonia, previtellogenic and early vitellogenic oocytes. A role for PK in M. rosenbergii reproduction was supported following experimental administration of MroPK to ovarian explant cultures, which led to an increase in the production of progesterone and estradiol and upregulation of expression of steroidogenesis-related genes (3β-HSD and 17β-HSD) and vitellogenin (Vg). Together, these results support a role for MroPK in regulating ovarian maturation via steroidogenesis.

Selenium (Se) is a trace element with a narrow margin between beneficial effects and stress from toxic effects. The determinants of the transition from selenium adequacy to toxicity remain unknown. Moreover, the roles of selenoproteins and other adaptive responses also remain unclear. The effects of dynamic and localized redox fluctuations on survival and neurodegeneration also require further investigation. To better understand the underlying mechanisms, several studies utilized the nematode Caenorhabditis elegans (C. elegans) as a model. This review systematically addresses pivotal mechanistic controversies. Thioredoxin reductase-1 (TRXR-1) is the only protein in a small amount of the selenoproteome, and it also has a fully conserved selenocysteine insertion mechanism. Moreover, this systematic review also incorporates the current understanding of the molecular factors that determine selenium homeostasis, ranging from neurotoxicological diseases to biosynthetic circumstances. TRXR-1 supports health benefits such as enhance lipid metabolism, longevity, and stress response. During acute selenium toxicity, TRXR-1 is not needed for survival. Instead, cells defend against adverse effects by using the HIF-1 pathway. Reactive oxygen species (ROS) and hydrogen sulfide (H₂S) inhibit the prolyl hydroxylase EGL-9 in high-selenium conditions, stabilizing HIF-1 and initiating a transcriptional detoxification process independent of the selenoprotein mechanism. Finally, this review also discuss selective neurotoxicity, a condition in which degeneration that occurs solely in cholinergic ventral cord motor neurons plays a distinctive and precarious role among trace elements.

Background: Hypoxia-induced oxidative stress and ferroptosis contribute to blood–brain barrier dysfunction and neurovascular injury associated with ischemic stroke and neurodegenerative diseases. Luteolin, a naturally occurring flavonoid with potent antioxidant and anti-inflammatory activities, has emerged as a potential neuroprotective agent; however, its effects on hypoxia-induced ferroptosis in brain microvascular endothelial cells remain unclear. This study investigated the protective effects of luteolin and its association with changes in the PPARγ/FABP5/ALOX15 signaling pathway during hypoxia-induced ferroptotic injury. Methods: Human brain microvascular endothelial cells (HBEC-5i) were exposed to cobalt chloride (CoCl₂) to establish an in vitro hypoxia model and subsequently treated with luteolin. Cell viability was assessed using the MTT assay. Intracellular Fe²⁺ accumulation, reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH/GSSG) levels were determined using biochemical assays. The expression of ferroptosis- and hypoxia-related proteins, including GPX4, ALOX15, FABP5, PPARγ, HIF-1α, and VEGF, was evaluated by Western blotting. Results: CoCl₂-induced hypoxia significantly reduced cell viability and increased intracellular Fe²⁺ accumulation, ROS generation, lipid peroxidation, and ferroptosis-associated signaling in HBEC-5i cells. Hypoxic conditions upregulated ALOX15 and FABP5 expression while suppressing GPX4 and PPARγ levels. Luteolin treatment markedly attenuated these effects by restoring GSH/GSSG homeostasis, enhancing GPX4 expression, reducing ALOX15-mediated lipid peroxidation, and suppressing HIF-1α and VEGF expression. In addition, luteolin modulated the PPARγ/FABP5 signaling pathway, suggesting its involvement in the regulation of hypoxia-induced ferroptosis. Conclusions: Luteolin attenuates hypoxia-induced ferroptosis-associated changes in human brain microvascular endothelial cells by restoring redox homeostasis and is associated with coordinated modulation of the PPARγ/FABP5/ALOX15 pathway. These findings extend previous reports of the anti-ferroptotic effects of luteolin by providing evidence in brain microvascular endothelial cells under hypoxia-mimetic stress.