Free Radic Biol Med
November 2024
Objectives: This study aims to elucidate the role of Fe overload in kainic acid (KA)-induced excitotoxicity, investigate the involvement of ferritinophagy selective cargo receptor NCOA4 in the pathogenesis of excitotoxicity.
Methods: Western blotting was used to detect the expression of FTH1, NCOA4, Lamp2, TfR, FPN, and DMT1 after KA stereotaxic injection into the unilateral striatum of mice. Colocalization of Fe with lysosomes in KA-treated primary cortical neurons was observed by using confocal microscopy.
As a major contributor to neonatal death and neurological sequelae, hypoxic-ischemic encephalopathy (HIE) lacks a viable medication for treatment. Oxidative stress induced by hypoxic-ischemic brain damage (HIBD) predisposes neurons to ferroptosis due to the fact that neonates accumulate high levels of polyunsaturated fatty acids for their brain developmental needs but their antioxidant capacity is immature. Ferroptosis is a form of cell death caused by excessive accumulation of iron-dependent lipid peroxidation and is closely associated with mitochondria.
View Article and Find Full Text PDFNeurons rely heavily on high mitochondrial metabolism to provide sufficient energy for proper development. However, it remains unclear how neurons maintain high oxidative phosphorylation (OXPHOS) during development. Mitophagy plays a pivotal role in maintaining mitochondrial quality and quantity.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Biochem Biophys Res Commun
October 2024
Exercise is known to be an effective intervention for depression. NADPH has been demonstrated to have neuroprotective effects in our previous studies. This study aimed to investigate if NADPH has antidepressant effects and can mimic the effects of exercise in a chronic unpredictable stress (CUS) rat model.
View Article and Find Full Text PDFHypoxia-ischemia (HI) is one of the main causes of neonatal brain injury. Mitophagy has been implicated in the degradation of damaged mitochondria and cell survival following neonatal brain HI injury. Pleckstrin homology-like domain family A member 1 (PHLDA1) plays vital roles in the progression of various disorders including the regulation of oxidative stress, the immune responses and apoptosis.
View Article and Find Full Text PDFIschemic heart disease invariably leads to devastating damage to human health. Nicotinamide ribose (NR), as one of the precursors of NAD synthesis, has been discovered to exert a protective role in various neurological and cardiovascular disorders. Our findings demonstrated that pretreatment with 200 mg/kg NR for 3 h significantly reduced myocardial infarct area, decreased levels of CK-MB and LDH in serum, and improved cardiac function in the rats during myocardial ischemia-reperfusion (I/R) injury.
View Article and Find Full Text PDFObesity is one of the most common metabolic diseases around the world, which is distinguished by the abnormal buildup of triglycerides within adipose cells. Recent research has revealed that autophagy regulates lipid mobilization to maintain energy balance. TIGAR (Trp53 induced glycolysis regulatory phosphatase) has been identified as a glycolysis inhibitor, whether it plays a role in the metabolism of lipids is unknown.
View Article and Find Full Text PDFAutophagy involves the sequestration and delivery of cytoplasmic materials to lysosomes, where proteins, lipids, and organelles are degraded and recycled. According to the way the cytoplasmic components are engulfed, autophagy can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy. Recently, many studies have found that autophagy plays an important role in neurological diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, neuronal excitotoxicity, and cerebral ischemia.
View Article and Find Full Text PDFBackground: Although depression has been a serious neuropsychiatric disorder worldwide, current antidepressants used in clinical practice have various weaknesses, including delayed onset and low rates of efficacy. Recently, the development of new antidepressants from natural herbal medicine has become one of the important research hotspots. Cucurbitacin B is a natural compound widely distributed in the Cucurbitaceae and Cruciferae families and has many pharmacological activities.
View Article and Find Full Text PDFEvidence from clinical studies and preclinical studies supports that exercise preconditioning can not only reduce the risk of stroke but also improve brain tissue and functional outcome after stroke. It has been demonstrated that autophagy and mitochondrial dynamics are involved in ischemic stroke. However, it is still unclear whether exercise preconditioning-induced neuroprotection against stroke is associated with modulation of autophagy and mitochondrial dynamics.
View Article and Find Full Text PDFIschemic stroke seriously threatens human health because of high rates of morbidity, mortality and disability. This study compared the effects of nicotinamide adenine dinucleotide (NAD) and butylphthalide (NBP) on and ischemic stroke models. Transient middle cerebral artery occlusion/reperfusion (t-MCAO/R) model was established in mice, and the cultured primary cortical neurons were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R).
View Article and Find Full Text PDFThe nicotinamide adenine dinucleotide (NAD/NADH) and nicotinamide adenine dinucleotide phosphate (NADP/NADPH) redox couples function as cofactors or/and substrates for numerous enzymes to retain cellular redox balance and energy metabolism. Thus, maintaining cellular NADH and NADPH balance is critical for sustaining cellular homeostasis. The sources of NADPH generation might determine its biological effects.
View Article and Find Full Text PDFCoenzyme I (nicotinamide adenine dinucleotide, NAD/NADH) and coenzyme II (nicotinamide adenine dinucleotide phosphate, NADPNADPH) are involved in various biological processes in mammalian cells. NAD is synthesised through the de novo and salvage pathways, whereas coenzyme II cannot be synthesised de novo. NAD is a precursor of coenzyme II.
View Article and Find Full Text PDFThe cell-to-cell transfer of α-synuclein (α-Syn) greatly contributes to Parkinson's disease (PD) pathogenesis and underlies the spread of α-Syn pathology. During this process, extracellular α-Syn can activate microglia and neuroinflammation, which plays an important role in PD. However, the effect of extracellular α-Syn on microglia autophagy is poorly understood.
View Article and Find Full Text PDFThe significant role of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) in signal transduction is mediated by the production of reactive oxygen species (ROS), especially in the central nervous system (CNS). The pathogenesis of some neurologic and psychiatric diseases is regulated by ROS, acting as a second messenger or pathogen. In the CNS, the involvement of Nox-derived ROS has been implicated in the regulation of multiple signals, including cell survival/apoptosis, neuroinflammation, migration, differentiation, proliferation, and synaptic plasticity, as well as the integrity of the blood/brain barrier.
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