NadPH AND Parkinsons

Neurite degeneration, a major component of many neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, is not part of the typical apoptosis signaling mechanism, but rather it appears that a self-destructive process is in action. Oxidative stress is a well-known inducer of neurodegenerative pathways: neuronal cell death and neurite degeneration. Although oxidative stress exerts cytotoxic effects leading to neuronal loss, the pathogenic mechanisms and precise signaling pathways by which oxidative stress causes neurite degeneration have remained entirely unknown...

In the present study, we aimed to investigate the role and mechanism of Parkinson's disease protein 7 (Park7) in myocardial infarction (MI). The Park7 expression in the serum and tissues was down-regulated in mice with MI. Recombinant Park7 protein protected against MI-induced injury and reduced oxidative stress in mice model. Conversely, knockout Park7 increased injury of MI and promoted oxidative stress in MI mice model. In embryonic rat cardiac myoblasts H9c2 cells, over-expression of Park7 reduced reactive oxygen species (ROS)-induced oxidative stress, while down-regulation of Park7 increased ROS-induced oxidative stress...

Dysfunctional mitochondrial quality control (MQC) is implicated in the pathogenesis of Parkinson's disease (PD). The improper selection of mitochondria for mitophagy increases reactive oxygen species (ROS) levels and lowers ATP levels. The downstream effects include oxidative damage, failure to maintain proteostasis and ion gradients, and decreased NAD+ and NADPH levels, resulting in insufficient energy metabolism and neurotransmitter synthesis. A ketosis-based metabolic therapy that increases the levels of (R)-3-hydroxybutyrate (BHB) may reverse the dysfunctional MQC by partially replacing glucose as an energy source, by stimulating mitophagy, and by decreasing inflammation...

Parkinson's Disease (PD) is a neurogenerative disorder characterized by the death of dopaminergic neurons in the Substantia Nigra pars compacta (SNpc), leading to motor, cognitive, learning, and respiratory dysfunctions. New evidence revealed that breathing impairment in PD mainly result from oxidative stress (OS) that starts apoptotic signaling in respiratory neurons. Here, we investigated the role of OS inhibition using apocynin (NADPH oxidase non-specific inhibitor) in a 6-OHDA animal model of PD in the neural control of breathing...

With the acceleration of population aging, nervous system diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), anxiety, depression, stroke, and traumatic brain injury (TBI) have become a huge burden on families and society. The mechanism of neurological disorders is complex, which also lacks effective treatment, so relevant research is required to solve these problems urgently. Given that oxidative stress-induced lipid peroxidation eventually leads to ferroptosis, both oxidative stress and ferroptosis are important mechanisms causing neurological disorders, targeting mediators of oxidative stress and ferroptosis have become a hot research direction at present...

Current treatment of Parkinson's disease (PD) ameliorates symptoms but fails to block disease progression. This study was conducted to explore the protective effects of SVHRSP, a synthetic heat-resistant peptide derived from scorpion venom, against dopaminergic neurodegeneration in experimental models of PD. Results showed that SVHRSP dose-dependently reduced the loss of dopaminergic neuron in the nigrostriatal pathway and motor impairments in both rotenone and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p)-induced mouse PD models...

Mitochondrial dysfunction and oxidative stress are strongly implicated in Parkinson's disease (PD) pathogenesis and there is evidence that mitochondrially-generated superoxide can activate NADPH oxidase 2 (NOX2). Although NOX2 has been examined in the context of PD, most attention has focused on glial NOX2, and the role of neuronal NOX2 in PD remains to be defined. Additionally, pharmacological NOX2 inhibitors have typically lacked specificity. Here we devised and validated a proximity ligation assay for NOX2 activity and demonstrated that in human PD and two animal models thereof, both neuronal and microglial NOX2 are highly active in substantia nigra under chronic conditions...

BACKGROUND: Pesticides are important biological agents that deter or kill pests. Globally, about 2 million tons of pesticides are being utilized each year which highlights their importance. Previous studies have suggested that high levels of pesticide exposure are associated with increased risk of chronic diseases, including cancers, cardiotoxicity, Parkinson's disease, diabetes mellitus, neurological deficits, birth defects, and reproductive disorders. Prometryn is a commonly used selective triazine herbicide, which is currently used as an alternative to atrazine-based products...

Mitochondrial dysfunction and nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) are the major sources of augmentation in free radical generation leading to neurodegeneration. Although NADPH oxidase involvement is reported in zinc (Zn)-induced neurodegeneration, contribution of the mitochondrial dysfunction and its association with NADPH oxidase are not known. Therefore, the study was aimed to decipher the role of mitochondrial dysfunction and its link with NADPH oxidase in Zn-induced Parkinsonism...

Oxidative stress is closely related to the pathogenesis of Parkinson's disease (PD), a typical neurodegenerative disease. NADPH oxidase 2 (NOX2) is involved in hydrogen peroxide (H2 O2 ) generation. Recently, we have reported that treatment with H2 O2 and PD toxins, including 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenylpyridin-1-ium (MPP+ ) and rotenone, induces neuronal apoptosis by inhibiting the mTOR pathway. Here, we show that treatment with 6-OHDA, MPP+ or rotenone induced H2 O2 generation by upregulating the levels of NOX2 and its regulatory proteins (p22phox , p40phox , p47phox , p67phox , and Rac1), leading to apoptotic cell death in PC12 cells and primary neurons...

The 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. Newly-recognized biosynthetic enzymes and genetically encoded biosensors help us better understand how cells maintain biosynthesis and distribution of compartmentalized NAD(H) and NADP(H) pools...

Parkinson's disease (PD) and essential tremor (ET) are two common adult-onset tremor disorders in which prevalence increases with age. PD is a neurodegenerative condition with progressive disability. In ET, neurodegeneration is not an established etiology. We sought to determine whether an underlying metabolic pattern may differentiate ET from PD. Circulating metabolites in plasma and cerebrospinal fluid (CSF) were analyzed using gas chromatography-mass spectroscopy. There were several disrupted pathways in PD compared to ET plasma including glycolysis, tyrosine, phenylalanine, tyrosine biosynthesis, purine and glutathione metabolism...

Rotigotine is a non-ergoline dopamine agonist that has been licensed for the treatment of Parkinson's disease. Cardiovascular diseases are the world's leading cause of death. Ox-LDL- induced endothelial damages are involved in the initiation and progression of cardiovascular diseases. In this study, we assessed the beneficial properties of Rotigotine on ox-LDL-induced insults to HUVECs to highlight its potential use in the treatment of cardiovascular diseases. Our findings show that Rotigotine suppresses the expressions of low-density lipoprotein receptor (LDL-R), proprotein convertase subtilisin/kexin type 9 (PCSK-9), and sterol regulatory element-binding protein (SREBP-2)...

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by neuronal loss and tissue atrophy mainly in the striatum and cortex. In the early stages of the disease, impairment of neuronal function, synaptic dysfunction and white matter loss precedes neuronal death itself. Relative to other neurodegenerative diseases such as Alzheimer's and Parkinson's disease and Amyotrophic Lateral Sclerosis, where the effects of either microglia or NADPH oxidases (NOXs) are recognized as important contributors to disease pathogenesis and progression, there is a pronounced lack of information in HD...

Background: Achyranthes bidentata polypeptide fraction k (ABPPk) has been shown to protect ischemic stroke and Parkinson's disease, and can inhibit neuroinflammation in lipopolysaccharide (LPS)-activated BV2 microglia. However, the effect of ABPPk responsible for alleviating microglial neurotoxicity remains unknown. Methods: Primary microglia were cultured to investigate the effect of ABPPk on LPS-induced neuroinflammation. Microglia conditioned medium (MCM) was collected to stimulate primary cortical neurons and then the neuronal viability, lactate dehydrogenase (LDH) release, intracellular calcium influx, mitochondria membrane potential (MMP) were assessed, respectively...

Macroautophagy/autophagy is an evolutionarily well-conserved recycling process in response to stress conditions, including a burst of reactive oxygen species (ROS) production. High level of ROS attack key cellular macromolecules. Protein cysteinyl thiols or non-protein thiols as the major redox-sensitive targets thus constitute the first-line defense. Autophagy is unique, because it removes not only oxidized/damaged proteins but also bulky ROS-generating organelles (such as mitochondria and peroxisome) to restrict further ROS production...

Most steroidogenesis disorders are caused by mutations in genes encoding the steroidogenic enzymes, but work in the past 20 years has identified related disorders caused by mutations in the genes encoding the cofactors that transport electrons from NADPH to P450 enzymes. Most P450s are microsomal and require electron donation by P450 oxidoreductase (POR); by contrast, mitochondrial P450s require electron donation via ferredoxin reductase (FdxR) and ferredoxin (Fdx). POR deficiency is the most common and best-described of these new forms of congenital adrenal hyperplasia...

Neuroinflammation plays an important role in neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease. HACE1 (HECT domain and Ankyrin repeat Containing E3 ubiquitin-protein ligase 1) is a tumor suppressor. Recent evidence suggests that HACE1 may be involved in oxidative stress responses. Due to the critical role of ROS in neuroinflammation, we speculated that HACE1 might participate in neuroinflammation and related neurodegenerative diseases, such as PD. In this study, we investigated the role of HACE1 in neuroinflammation of PD models...

Oxidative stress plays an important role in the degeneration of dopaminergic neurons, which causes Parkinson's disease (PD). Oxidative stress products, antioxidant and their balance have important roles in the development of oxidative stress-based PD. The impact of reactive oxygen species (ROS) and defence systems can be altered by genetic polymorphisms, and thus the risk of PD may also be affected. We aimed to investigate the possible association of individual susceptibility with the development of oxidative stress-based PD...

Dysregulation of the tissue renin-angiotensin system (RAS) is involved in tissue oxidative and inflammatory responses. Among RAS components, renin, its precursor (pro)renin and its specific receptor (PRR) have been less investigated, particularly in the brain. We previously showed the presence of PRR in neurons and glial cells in the nigrostriatal system of rodents and primates, including humans. Now, we used rat and mouse models and cultures of BV2 and primary microglial cells to study the role of PRR in microglial pro-inflammatory responses...