Nitric Oxide, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Molecular Psychiatry, Год журнала: 2024, Номер unknown
Опубликована: Сен. 2, 2024
Abstract Normal brain functioning relies on high aerobic energy production provided by mitochondria. Failure to supply a sufficient amount of energy, seen in different disorders, including autism spectrum disorder (ASD), may have significant negative impact development and support functions. Mitochondrial dysfunction, manifested the abnormal activities electron transport chain impaired metabolism, greatly contributes ASD. The aberrant this organelle is such importance that ASD has been proposed as mitochondrial disease. It should be noted not only function In particular, these organelles are involved regulation Ca 2+ homeostasis, mechanisms programmed cell death, autophagy, reactive oxygen nitrogen species (ROS RNS) production. Several syndromes originated from mitochondria-related mutations display phenotype. Abnormalities handling ATP mitochondria affect synaptic transmission, plasticity, development, contributing ROS regulate activity permeability transition pore (mPTP). prolonged opening affects redox state mitochondria, impairs oxidative phosphorylation, activates apoptosis, ultimately leading death. A dysregulation between enhanced processes apoptosis inhibited autophagy leads accumulation toxic products brains individuals with Although many still investigated, whether they cause or consequence unknown, accumulating data show breakdown any functions contribute review, we discuss multifaceted role various aspects neuroscience.
Язык: Английский
Процитировано
8
Translational Psychiatry, Год журнала: 2025, Номер 15(1)
Опубликована: Март 26, 2025
Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized by early molecular events that influence progression. Still, mechanisms caused different mutations of AD are not understood. We have performed a multidisciplinary study to investigate and compare stages pathology in two transgenic mouse models: P301S 5xFAD. Using SNOTRAP-based mass spectrometry, we assessed changes S-nitrosylation, nitric oxide-mediated post-translational modification, proteins both models during their juvenile age. The increased levels 3-nitrotyrosine confirmed nitrosative stress mutant mice. Systems biology analysis revealed shared processes between models, particularly γ-aminobutyric acid (GABA)ergic glutamatergic neurotransmission processes. In model, identified 273 S-nitrosylated (SNOed) cortex, with 244 uniquely SNOed diseased 5xFAD 309 were identified. found altered expression glutamate/GABA-related markers cortex hippocampus models. Additionally, phosphorylation mTOR signaling components hyperactivation this pathway Conversely, mice showed no significant except for elevated ribosomal protein S6 cortex. Our findings key stages. These could serve as potential biomarkers therapeutic targets early-stage AD.
Язык: Английский
Процитировано
0
Nitric Oxide, Год журнала: 2024, Номер 153, С. 26 - 40
Опубликована: Окт. 5, 2024
Язык: Английский
Процитировано
3
Journal of Molecular Neuroscience, Год журнала: 2024, Номер 74(4)
Опубликована: Сен. 30, 2024
Язык: Английский
Процитировано
2
Brain Research, Год журнала: 2024, Номер 1846, С. 149251 - 149251
Опубликована: Окт. 9, 2024
Язык: Английский
Процитировано
1
Опубликована: Янв. 1, 2024
Autism spectrum disorder (ASD) is a complex neurodevelopmental characterized by difficulties in social interaction and communication, repetitive behaviors, restricted interests. Over time, the prevalence of ASD increasing, reaching 2% population to date. Unfortunately, underlying molecular mechanism behind remains unknown. Therefore, there no FDA-approved drug for treatment, It has been reported that oxidative nitrosative stress are strongly linked ASD. We have recently found nitric oxide (NO•) NO•-meditated post-transitional modifications play key role One proteins affected affecting NO• thioredoxin (Trx). Here we show Trx antioxidant system may crucial pathology. hypothesize altered Shank3 KO mouse model autism, which lead decreased activity nuclear factor erythroid 2-related 2 (Nrf2), leading stress, thus, contributing ASD-related phenotypes. To test this hypothesis, conducted vivo behavioral studies used primary cortical neurons derived from mutant mice as well human SH-SY5Y with SHANK3 mutation. showed significant changes levels redox mice. A Trx1 inhibitor PX-12 Nrf2 expression wild-type mice, causing abnormal alterations synaptic neurotransmission markers, an elevation stress. The tests revealed inhibition results ASD-like phenotype, similar observed autism. Our findings confirm strong link between ASD, including increased oxidative/nitrosative impaired phenotype. study pave way developing new treatments.
Язык: Английский
Процитировано
0
Pharmaceuticals, Год журнала: 2024, Номер 17(9), С. 1203 - 1203
Опубликована: Сен. 12, 2024
We have previously observed that
Язык: Английский
Процитировано
0
Brain Communications, Год журнала: 2024, Номер 6(5)
Опубликована: Янв. 1, 2024
Abstract Early childhood exposure to general anaesthesia has been linked potential changes in infant brain morphology and behaviour preclinical studies, contributing long-term behaviours associated with autism spectrum disorder. This study investigates the association between early risk of autism, using a population-based cohort matching for baseline characteristics evaluates effect sevoflurane on autism-like mice, Taiwan Maternal Child Health Database. Children aged 0–3 who received at least one 2004 2014 were matched 1:1 children not exposed. Risk ratios confidence intervals used assess relationship occurrence autism. Additionally, mice exposed 2 h postnatal days 5–7, related evaluated. Propensity score resulted 7530 each group. The incidence rates (IRs) 11.26 6.05 per 100 000 person-years unexposed groups, respectively. ratio following was 1.86 (95% interval, 1.34–2.59). In induced led downregulation high-risk genes, including ARID1B, GABRA5, GABRB3, GRIN2B, SHANK3 SUV420H1. is an increased Repeated induces behaviours, suggesting link development
Язык: Английский
Процитировано
0
Nitric Oxide, Год журнала: 2024, Номер 153, С. 41 - 49
Опубликована: Окт. 9, 2024
Язык: Английский
Процитировано
0
Nitric Oxide, Год журнала: 2024, Номер unknown
Опубликована: Ноя. 1, 2024
Язык: Английский
Процитировано
0