The Role of Thioredoxin System in Shank3 Mouse Model of Autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by difficulties in social interaction and communication, repetitive behaviors, and restricted interests. Unfortunately, the underlying molecular mechanism behind ASD remains unknown. It has been reported that oxidative and nitrosative stress are strongly linked to ASD.

The multifaceted role of mitochondria in autism spectrum disorder.

Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different brain disorders, including autism spectrum disorder (ASD), may have a significant negative impact on brain development and support of different brain functions. Mitochondrial dysfunction, manifested in the abnormal activities of the electron transport chain and impaired energy metabolism, greatly contributes to ASD.

Renal Mitochondrial ATP Transporter Ablation Ameliorates Obesity-Induced CKD.

Significance Statement: This study sheds light on the central role of adenine nucleotide translocase 2 (ANT2) in the pathogenesis of obesity-induced CKD. Our data demonstrate that ANT2 depletion in renal proximal tubule cells (RPTCs) leads to a shift in their primary metabolic program from fatty acid oxidation to aerobic glycolysis, resulting in mitochondrial protection, cellular survival, and preservation of renal function. These findings provide new insights into the underlying mechanisms of obesity-induced CKD and have the potential to be translated toward the development of targeted therapeutic strategies for this debilitating condition.

Mutations associated with autism lead to similar synaptic and behavioral alterations in both sexes of male and female mouse brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder based on synaptic abnormalities. The estimated prevalence rate of male individuals diagnosed with ASD prevails over females is in a proportion of 4:1. Consequently, males remain the main focus in ASD studies in clinical and experimental settings.

Nitric Oxide Synthase Inhibition Prevents Cell Proliferation in Glioblastoma.

Glioblastoma multiforme (GBM) is a prevalent and aggressive primary brain tumor, presenting substantial treatment challenges and high relapse rates. GBM is characterized by alterations in molecular signaling and enzyme expression within malignant cells. This tumor exhibits elevated nitric oxide (NO) levels.

Effects of extended-release 7-nitroindazole gel formulation treatment on the behavior of Shank3 mouse model of autism.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by behavioral deficits such as abnormalities in communication, social interaction, anxiety, and repetitive behavior. We have recently shown that the Shank3 mutation in mice representing a model of ASD causes excessive nitric oxide (NO) levels and aberrant protein S-nitrosylation. Further, 10-day daily injections of 7-NI, a neuronal nitric oxide synthase inhibitor, into Shank3 and Cntnap2 mutant mice (models of ASD) at a dose of 80 mg/kg reversed the manifestations of ASD phenotype.

The NO Answer for Autism Spectrum Disorder.

Autism spectrum disorders (ASDs) include a wide range of neurodevelopmental disorders. Several reports showed that mutations in different high-risk ASD genes lead to ASD. However, the underlying molecular mechanisms have not been deciphered.

Mechanistic insight into female predominance in Alzheimer's disease based on aberrant protein S-nitrosylation of C3.

Protein S-nitros(yl)ation (SNO) is a posttranslational modification involved in diverse processes in health and disease and can contribute to synaptic damage in Alzheimer's disease (AD). To identify SNO proteins in AD brains, we used triaryl phosphine (TRAP) combined with mass spectrometry (MS). We detected 1449 SNO proteins with 2809 SNO sites, representing a wide range of S-nitrosylated proteins in 40 postmortem AD and non-AD human brains from patients of both sexes.

A cross-talk between nitric oxide and the glutamatergic system in a Shank3 mouse model of autism.

Nitric oxide (NO) is a multifunctional signaling molecule that plays a crucial role in synaptic transmission and neuronal function. Pioneering studies show that nitric oxide (NO) and S-nitrosylation (SNO, the NO-mediated posttranslational modification) can engender nitrosative stress in the brain, contributing to neurodegenerative diseases. Little is known, however, about the aberrant NO signaling in neurodevelopmental disorders including autism spectrum disorder (ASD).

Arsenic alters nitric oxide signaling similar to autism spectrum disorder and Alzheimer's disease-associated mutations.

Epidemiological studies have proven that exposure to Arsenic (AS) leads to the development of many neurological disorders. However, few studies have investigated its molecular mechanisms in the brain. Our previous work has revealed nitric oxide (NO)-mediated apoptosis and SNO reprogramming in the cortex following arsenic treatment, yet the role of NO and S-nitrosylation (SNO) in AS-mediated neurotoxicity has not been investigated.

Proteomics of autism and Alzheimer's mouse models reveal common alterations in mTOR signaling pathway.

Autism spectrum disorder (ASD) and Alzheimer's disease (AD) are two different neurological disorders that share common clinical features, such as language impairment, executive functions, and motor problems. A genetic convergence has been proposed as well. However, the molecular mechanisms of these pathologies are still not well understood.

Preconditioning or Postconditioning with 8-Br-cAMP-AM Protects the Heart against Regional Ischemia and Reperfusion: A Role for Mitochondrial Permeability Transition.

The cAMP analogue 8-Br-cAMP-AM (8-Br) confers marked protection against global ischaemia/reperfusion of isolated perfused heart. We tested the hypothesis that 8-Br is also protective under clinically relevant conditions (regional ischaemia) when applied either before ischemia or at the beginning of reperfusion, and this effect is associated with the mitochondrial permeability transition pore (MPTP). 8-Br (10 μM) was administered to Langendorff-perfused rat hearts for 5 min either before or at the end of 30 min regional ischaemia.

Systems Biology Reveals S-Nitrosylation-Dependent Regulation of Mitochondrial Functions in Mice with Mutation Associated with Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder manifested in repetitive behavior, abnormalities in social interactions, and communication. The pathogenesis of this disorder is not clear, and no effective treatment is currently available. Protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification, targets key proteins implicated in synaptic and neuronal functions.

Regional Differences in S-Nitrosylation in the Cortex, Striatum, and Hippocampus of Juvenile Male Mice.

Nitric oxide (NO) is a multifunctional neurotransmitter that plays a major role in neuronal and synaptic functions. S-nitrosylation (SNO), the NO-mediated protein posttransitional modification (PTM), is known to regulate physiological and pathological processes in the brain. However, the physiological role in different neuroanatomical brain regions has not been well investigated.

Systems biology reveals reprogramming of the S-nitroso-proteome in the cortical and striatal regions of mice during aging process.

Cell aging depends on the rate of cumulative oxidative and nitrosative damage to DNA and proteins. Accumulated data indicate the involvement of protein S-nitrosylation (SNO), the nitric oxide (NO)-mediated posttranslational modification (PTM) of cysteine thiols, in different brain disorders. However, the changes and involvement of SNO in aging including the development of the organism from juvenile to adult state is still unknown.

Low Doses of Arsenic in a Mouse Model of Human Exposure and in Neuronal Culture Lead to S-Nitrosylation of Synaptic Proteins and Apoptosis via Nitric Oxide.

Background: Accumulating public health and epidemiological literature support the hypothesis that arsenic in drinking water or food affects the brain adversely.

Methods: Experiments on the consequences of nitric oxide (NO) formation in neuronal cell culture and mouse brain were conducted to probe the mechanistic pathways of nitrosative damage following arsenic exposure.

Results: After exposure of mouse embryonic neuronal cells to low doses of sodium arsenite (SA), we found that Ca was released leading to the formation of large amounts of NO and apoptosis.

The role of nitric oxide in brain disorders: Autism spectrum disorder and other psychiatric, neurological, and neurodegenerative disorders.

Nitric oxide (NO) is a multifunctional signalling molecule and a neurotransmitter that plays an important role in physiological and pathophysiological processes. In physiological conditions, NO regulates cell survival, differentiation and proliferation of neurons. It also regulates synaptic activity, plasticity and vesicle trafficking.

Sex Differences in Biological Processes and Nitrergic Signaling in Mouse Brain.

Nitric oxide (NO) represents an important signaling molecule which modulates the functions of different organs, including the brain. S-nitrosylation (SNO), a post-translational modification that involves the binding of the NO group to a cysteine residue, is a key mechanism of nitrergic signaling. Most of the experimental studies are carried out on male animals.

S-nitrosylation of E3 ubiquitin-protein ligase RNF213 alters non-canonical Wnt/Ca+2 signaling in the P301S mouse model of tauopathy.

Mutations in the MAPT gene, which encodes the tau protein, are associated with several neurodegenerative diseases, including frontotemporal dementia (FTD), dementia with epilepsy, and other types of dementia. The missense mutation in the Mapt gene in the P301S mouse model of FTD results in impaired synaptic function and microgliosis at three months of age, which are the earliest manifestations of disease. Here, we examined changes in the S-nitrosoproteome in 2-month-old transgenic P301S mice in order to detect molecular events corresponding to early stages of disease progression.

Associations of diet and lifestyle factors with common volatile organic compounds in exhaled breath of average-risk individuals.

Background: Detection of diseases via exhaled breath remains an attractive idea despite persisting gaps in understanding the origin of volatile organic compounds (VOCs) and their relationship with the disease of interest. Data on factors potentially influencing the results of breath analysis remain rather sparse and often controversial. In this study, we aimed to investigate the associations of common VOCs in exhaled breath of average-risk individuals with socio-demographic and lifestyle factors, medical conditions as well as diet.

Shank3 mutation in a mouse model of autism leads to changes in the S-nitroso-proteome and affects key proteins involved in vesicle release and synaptic function.

Mutation in the SHANK3 human gene leads to different neuropsychiatric diseases including Autism Spectrum Disorder (ASD), intellectual disabilities and Phelan-McDermid syndrome. Shank3 disruption in mice leads to dysfunction of synaptic transmission, behavior, and development. Protein S-nitrosylation, the nitric oxide (NO)-mediated posttranslational modification (PTM) of cysteine thiols (SNO), modulates the activity of proteins that regulate key signaling pathways.

Diagnosis and Classification of 17 Diseases from 1404 Subjects via Pattern Analysis of Exhaled Molecules.

We report on an artificially intelligent nanoarray based on molecularly modified gold nanoparticles and a random network of single-walled carbon nanotubes for noninvasive diagnosis and classification of a number of diseases from exhaled breath. The performance of this artificially intelligent nanoarray was clinically assessed on breath samples collected from 1404 subjects having one of 17 different disease conditions included in the study or having no evidence of any disease (healthy controls). Blind experiments showed that 86% accuracy could be achieved with the artificially intelligent nanoarray, allowing both detection and discrimination between the different disease conditions examined.