NadPH AND Parkinsons

Apart from dopaminergic neurotoxicity, exposure to rotenone, a commonly used insecticide in agriculture, also adversely affects hippocampal and cortical neurons, resulting in cognitive impairments in mice. We recently established a role of microglia-mediated neuroinflammation in rotenone-elicited deficits of cognition, yet the mechanisms remain elusive. Here, we investigated the involvement of NADPH oxidase 2 (NOX2) catalytic subunit gp91phox in rotenone-induced cognitive deficits and the associated mechanisms...

The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system...

Parkinson's disease (PD) is a neurodegenerative disease, whereby disturbances within the antioxidant defence system, increased aggregation of proteins, and activation of neuronal apoptosis all have a crucial role in the pathogenesis. In this context, exploring the neuroprotective capabilities of compounds that sustain the effectiveness of cellular defence systems in neurodegenerative disorders is worthwhile. During this study, we assessed how 6-hydroxy-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline (HTHQ), which has antioxidant properties, affects the functioning of the antioxidant system, the activity of NADPH-generating enzymes and chaperones, and the level of apoptotic processes in rats with rotenone-induced PD...

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system...

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+ ), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)...

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and the most common movement disorder. Although PD etiology is not fully understood, alpha (α)-synuclein is a key protein involved in PD pathology. MicroRNAs (miRNA), small gene regulatory RNAs that control gene expression, have been identified as biomarkers and potential therapeutic targets for brain diseases, including PD. In particular, miR-124 is downregulated in the plasma and brain samples of PD patients. Recently we showed that the brain delivery of miR-124 counteracts 6-hydroxydopamine-induced motor deficits...

The brain renin-angiotensin system (RAS) has been related to dopaminergic degeneration, and high expression of the angiotensin II (AngII) type 1 receptor (AT1) gene is a marker of the most vulnerable neurons in humans. However, it is unknown whether AngII/AT1 overactivation affects α-synuclein aggregation and transmission. In vitro, AngII/AT1 activation increased α-synuclein aggregation in dopaminergic neurons and microglial cells, which was related to AngII-induced NADPH-oxidase activation and intracellular calcium raising...

Parkinson's disease (PD) is a common neurodegenerative disorder with a complicated etiology and pathogenesis. α-Synuclein aggregation, dopaminergic (DA) neuron loss, mitochondrial injury, oxidative stress, and inflammation are involved in the process of PD. Neuroinflammation has been recognized as a key element in the initiation and progression of PD. In this review, we summarize the inflammatory response and pathogenic mechanisms of PD. Additionally, we describe the potential anti-inflammatory therapies, including nod-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome inhibition, nuclear factor κB (NF-κB) inhibition, microglia inhibition, astrocyte inhibition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition, the peroxisome proliferator-activated receptor γ (PPARγ) agonist, targeting the mitogen-activated protein kinase (MAPK) pathway, targeting the adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway, targeting α-synuclein, targeting miRNA, acupuncture, and exercise...

Diseases like Alzheimer's and Parkinson's diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions...

Several studies showed an association between metabolic syndrome (MetS) and Parkinson's disease (PD). The linking mechanisms remain unclear. MetS promotes low-grade peripheral oxidative stress and inflammation and dysregulation of the adipose renin-angiotensin system (RAS). Interestingly, brain RAS dysregulation is involved in the progression of dopaminergic degeneration and PD. Circulating extracellular vesicles (EVs) from MetS fat tissue can cross the brain-blood barrier and may act as linking signals. We isolated and characterized EVs from MetS and control rats and analyzed their mRNA and protein cargo using RT-PCR and the ExoView R200 platform, respectively...

According to recent research, selective neuronal vulnerability in Parkinson's disease (PD) results from several phenotypic traits, including calcium-dependent, feed-forward control of mitochondrial respiration leading to elevated reactive oxygen species and cytosolic calcium concentration, an extensive axonal arbor, and a reactive neurotransmitter. Therefore, antioxidant therapy is a promising direction in the treatment of PD. In vitro studies have indicated the survival-promoting activity of bacterial melanin (BM) on midbrain dopaminergic neuron cultures...

The brainstem pedunculopontine (PPN) and laterodorsal tegmental (LDTg) nuclei are involved in multifarious activities, including motor control. Yet, their exact cytoarchitectural boundaries are still uncertain. We therefore initiated a comparative study of the topographical and neurochemical organization of the PPN and LDTg in cynomolgus monkeys (Macaca fascicularis) and humans. The distribution and morphological characteristics of neurons expressing choline acetyltransferase (ChAT) and/or nicotinamide adenine dinucleotide phosphate diaphorase (Nadph-δ) were documented...

Ferroptosis, a new type of cell death accompanied by iron accumulation and lipid peroxidation, is implicated in the pathology of Parkinson's disease (PD), which is a prevalent neurodegenerative disorder that primarily occurred in the elderly population. Epigallocatechin-3-gallate (EGCG) is the major polyphenol in green tea with known neuroprotective effects in PD patients. But whether EGCG-mediated neuroprotection against PD involves regulation of ferroptosis has not been elucidated. In this study, we established a PD model using PINK1 mutant Drosophila...

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes -to- Bacteroidetes ratio and the abundances of Enterococcus , Streptococcus , Bacteroides and Lactobacillus genera , which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation...

The renin angiotensin system (RAS) has several components including signaling peptides, enzymes, and membrane receptors. The effort in characterizing this system in the periphery has led to the approval of a class of antihypertensives. Much less is known about RAS in the central nervous system. The production of RAS peptides and the expression of several RAS enzymes and receptors in dopaminergic neurons of the substantia nigra has raised expectations in the therapy of Parkinson's disease, a neurodegenerative condition characterized by lack of dopamine in the striatum, the motor control region of the mammalian brain...

Neurodegenerative diseases (NDDs) causing cognitive impairment and dementia are difficult to treat due to the lack of understanding of primary initiating factors. Meanwhile, major sporadic NDDs share many risk factors and exhibit similar pathologies in their early stages, indicating the existence of common initiation pathways. Glucose hypometabolism associated with oxidative stress is one such primary, early and shared pathology, and a likely major cause of detrimental disease-associated cascades; targeting this common pathology may therefore be an effective preventative strategy for most sporadic NDDs...

Oxidative stress-mediated damage is often a downstream result of Parkinson's disease (PD), which is marked by sharp decline in dopaminergic neurons within the nigrostriatal regions of the brain, accounting for the symptomatic motor deficits in patients. Regulating the level of oxidative stress may present a beneficial approach in preventing PD pathology. Here, we assessed the efficacy of a nicotinamide adenine phosphate (NADPH) oxidase (NOX) inhibitor, an exogenous reactive oxygen species (ROS) regulator synthesized by Aptabio therapeutics with the specificity to NOX-1, 2 and 4...

The pathophysiology of different neurodegenerative illnesses is significantly influenced by the polarization regulation of microglia and macrophages. Traditional classifications of macrophage phenotypes include the pro-inflammatory M1 and the anti-inflammatory M2 phenotypes. Numerous studies demonstrated dynamic non-coding RNA modifications, which are catalyzed by microglia-induced neuroinflammation. Different nutraceuticals focus on the polarization of M1/M2 phenotypes of microglia and macrophages, offering a potent defense against neurodegeneration...

A physiological level of oxygen/nitrogen free radicals and non-radical reactive species (collectively known as ROS/RNS) is termed oxidative eustress or "good stress" and is characterized by low to mild levels of oxidants involved in the regulation of various biochemical transformations such as carboxylation, hydroxylation, peroxidation, or modulation of signal transduction pathways such as Nuclear factor-κB (NF-κB), Mitogen-activated protein kinase (MAPK) cascade, phosphoinositide-3-kinase, nuclear factor erythroid 2-related factor 2 (Nrf2) and other processes...

Recent studies showed increased expression of complements in various neurodegenerative diseases, including Alzheimer's and Parkinson's diseases. However, the mechanism regulating the expression of complements and their roles in the pathogenesis of neurodegeneration are unclear. We hypothesized that acute neuroinflammation increases the expression and activation of brain complements, which, in turn, participate in chronic neuroinflammation and progressive neurodegeneration. We initially focused on the complement component C3, because C3 can activate microglia by binding to C3 receptors and attaching to damaged neurons destined to be phagocytosed by microglia...