Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 1819 - 1819

Published: Jan. 17, 2023

Autism spectrum disorder (ASD) is a heterogeneous, behaviorally defined neurodevelopmental disorder. Over the past two decades, prevalence of autism disorders has progressively increased, however, no clear diagnostic markers and specifically targeted medications for have emerged. As result, neurobehavioral abnormalities, neurobiological alterations in ASD, development novel ASD pharmacological therapy necessitate multidisciplinary collaboration. In this review, we discuss multiple animal models to contribute disease mechanisms as well new studies from disciplines assess behavioral pathology ASD. addition, summarize highlight mechanistic advances regarding gene transcription, RNA non-coding translation, abnormal synaptic signaling pathways, epigenetic post-translational modifications, brain-gut axis, immune inflammation neural loop abnormalities provide theoretical basis next step precision therapy. Furthermore, review existing tactics limits present challenges opportunities translating knowledge into clinical practice.

Language: Английский

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Oxidative damage in neurodegeneration: roles in the pathogenesis and progression of Alzheimer disease

Physiological Reviews, Journal Year: 2023, Volume and Issue: 104(1), P. 103 - 197

Published: Oct. 16, 2023

Alzheimer disease (AD) is associated with multiple etiologies and pathological mechanisms, among which oxidative stress (OS) appears as a major determinant. Intriguingly, OS arises in various pathways regulating brain functions, it seems to link different hypotheses mechanisms of AD neuropathology high fidelity. The particularly vulnerable damage, mainly because its unique lipid composition, resulting an amplified cascade redox reactions that target several cellular components/functions ultimately leading neurodegeneration. present review highlights the “OS hypothesis AD,” including amyloid beta-peptide-associated role protein oxidation unraveled by proteomics, antioxidant strategies have been investigated modulate progression AD. Collected studies from our groups others contributed unraveling close relationships between perturbation homeostasis elucidating redox-regulated events potentially involved both pathogenesis However, complexity requires in-depth understanding intracellular affecting relevant for functions. This crucial developing pharmacological targeting OS-mediated toxicity may contribute slow well improve quality life persons this severe dementing disorder.

Language: Английский

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Mitochondria and Brain Disease: A Comprehensive Review of Pathological Mechanisms and Therapeutic Opportunities

Biomedicines, Journal Year: 2023, Volume and Issue: 11(9), P. 2488 - 2488

Published: Sept. 7, 2023

Mitochondria play a vital role in maintaining cellular energy homeostasis, regulating apoptosis, and controlling redox signaling. Dysfunction of mitochondria has been implicated the pathogenesis various brain diseases, including neurodegenerative disorders, stroke, psychiatric illnesses. This review paper provides comprehensive overview intricate relationship between disease, focusing on underlying pathological mechanisms exploring potential therapeutic opportunities. The covers key topics such as mitochondrial DNA mutations, impaired oxidative phosphorylation, dynamics, calcium dysregulation, reactive oxygen species generation context disease. Additionally, it discusses emerging strategies targeting dysfunction, protective agents, metabolic modulators, gene therapy approaches. By critically analysing existing literature recent advancements, this aims to enhance our understanding multifaceted disease shed light novel interventions.

Language: Английский

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The role of oxidative stress in intervertebral disc degeneration: Mechanisms and therapeutic implications

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 98, P. 102323 - 102323

Published: May 9, 2024

Oxidative stress is one of the main driving mechanisms intervertebral disc degeneration(IDD). has been associated with inflammation in disc, cellular senescence, autophagy, and epigenetics cells. It above pathological are closely linked through common hub reactive oxygen species(ROS), promote each other process degeneration development disease. This reveals important role oxidative IDD, importance great potential IDD therapy targeting stress. The efficacy traditional unstable or cannot be maintained. In recent years, due to rise materials science, many bioactive functional have applied treatment combination drugs, satisfactory achieved. At present, research review antioxidant not complete. Based on existing studies, mechanism were summarized this paper, strategies based emerging reviewed.

Language: Английский

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Significance of Brain Glucose Hypometabolism, Altered Insulin Signal Transduction, and Insulin Resistance in Several Neurological Diseases

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: May 9, 2022

Several neurological diseases share pathological alterations, even though they differ in their etiology. Neuroinflammation, altered brain glucose metabolism, oxidative stress, mitochondrial dysfunction and amyloidosis are biological events found those disorders. Altered insulin-mediated signaling hypometabolism characteristic signs observed the brains of patients with certain diseases, but also others such as type 2 diabetes mellitus vascular diseases. Thus, significant reductions insulin receptor autophosphorylation Akt kinase activity, increased GSK-3 activity resistance, have been reported these contributing to decline cognitive function. Supporting this relationship is fact that nasal hippocampal administration has improve Additionally, precedes unmistakable clinical manifestations some by years, which may become a useful early biomarker. Deficiencies major pathways energy metabolism several supports hypothesis metabolic background. This review remarks on significance alterations keystone common pathogenic substrates for highlighting new potential targets.

Language: Английский

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Investigating the neuroprotective effects of Dracocephalum moldavica extract and its effect on metabolomic profile of rat model of sporadic Alzheimer's disease

Heliyon, Journal Year: 2025, Volume and Issue: 11(3), P. e42412 - e42412

Published: Feb. 1, 2025

Alzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target pathways presents potential gate for understanding and management AD. This study aimed to assess neuroprotective effects hydroalcoholic extract Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, putative metabolic in rat model AD induced intracerebroventricular streptozotocin (ICV-STZ). The DM was standardized quantified based examining total phenolic, flavonoid, rosmarinic acid, quercetin contents using colorimetry high-performance liquid chromatography (HPLC) methods. antioxidant evaluated 2,2-Diphenyl-1-picrylhydrazyl nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) induce sporadic (sAD) model. Following induction, orally administered (100, 200, 400 mg/kg/day) or donepezil (5 21 days. Cognitive function assessed radial arm water maze behavioral test. histopathological evaluations conducted cortex hippocampus regions. Matrix-assisted laser desorption/ionization-time flight mass spectrometry (MALDI-TOF MS) used metabolite changes various brain significantly attenuated dysfunction ICV-STZ according investigations. Thirty-two discriminating metabolites related amino acid metabolism; glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, prostaglandins), glucose identified brains sAD simultaneously first time this Polyphenols may contribute regulation these pathways. After treatment extract, 10 from 32 ones altered tissue sAD, most commonly at doses 200 mg/kg. In conclusion, demonstrates upregulation/downregulation pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, sphingomyelin sAD. These findings are consistent results outcomes.

Language: Английский

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Glial Cell Reprogramming in Ischemic Stroke: A Review of Recent Advancements and Translational Challenges

Translational Stroke Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

Language: Английский

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A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

Language: Английский

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NOX-induced oxidative stress is a primary trigger of major neurodegenerative disorders

Progress in Neurobiology, Journal Year: 2023, Volume and Issue: 231, P. 102539 - 102539

Published: Oct. 12, 2023

Neurodegenerative diseases (NDDs) causing cognitive impairment and dementia are difficult to treat due the lack of understanding primary initiating factors. Meanwhile, major sporadic NDDs share many risk factors exhibit similar pathologies in their early stages, indicating existence common initiation pathways. Glucose hypometabolism associated with oxidative stress is one such primary, shared pathology, a likely cause detrimental disease-associated cascades; targeting this pathology may therefore be an effective preventative strategy for most NDDs. However, its exact trigger remain unclear. Recent research suggests that caused by NADPH oxidase (NOX) activation mechanism among could prove long-sought ubiquitous NDD trigger. We focus on two - Alzheimer's disease (AD) Parkinson's (PD), as well acquired epilepsy which increasingly recognized comorbidity also discuss available data suggesting relevance proposed mechanisms other delve into commonalities these neuroinflammation NOX involvement identify potential therapeutic targets gain deeper underlying causes

Language: Английский

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The potential role of glucose metabolism, lipid metabolism, and amino acid metabolism in the treatment of Parkinson's disease

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 30(2)

Published: Aug. 14, 2023

Abstract Purpose of Review Parkinson's disease (PD) is a common neurodegenerative disease, which can cause progressive deterioration motor function causing muscle stiffness, tremor, and bradykinesia. In this review, we hope to describe approaches that improve the life PD patients through modifications energy metabolism. Recent Findings The main pathological features are loss nigrostriatal dopaminergic neurons production Lewy bodies. Abnormal aggregation α‐synuclein (α‐Syn) leading formation bodies closely associated with neuronal dysfunction degeneration. causes said be mitochondrial damage, oxidative stress, inflammation, abnormal protein aggregation. Presence metabolism another PD. Many studies have found significant differences between diseases metabolic decompensation, has become biological hallmark diseases. Summary highlight relationship (Glucose metabolism, lipid amino acid metabolism) Improvement key molecules in glucose fat (e.g., glucose‐6‐phosphate dehydrogenase, triglycerides, levodopa) might potentially beneficial Some these indicators may serve well during diagnosis addition, modulation pathways potential target for treatment prevention

Language: Английский

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