Versatile Copper-Chalcogenide-Based Nanoparticles for the Treatment of Brain Diseases

Nano Biomedicine and Engineering, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Язык: Английский

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Target oxidative stress-induced disulfidptosis: novel therapeutic avenues in Parkinson’s disease

Molecular Brain, Год журнала: 2025, Номер 18(1)

Опубликована: Апрель 4, 2025

Abstract Background Parkinson’s disease (PD), a globally prevalent neurodegenerative disorder, has been implicated with oxidative stress (OS) as central pathomechanism. Excessive reactive oxygen species (ROS) trigger neuronal damage and may induce disulfidptosis—a novel cell death modality not yet characterized in PD pathogenesis. Method Integrated bioinformatics analyses were conducted using GEO datasets to identify PD-associated differentially expressed genes (DEGs). These subjected to: immune infiltration analysis, gene set enrichment analysis (GSEA), weighted co-expression network (WGCNA), intersection of stress-related (ORGs) disulfidptosis-related (DRGs) for functional annotation. Following hub identification, diagnostic performance was validated independent cohorts. LASSO regression applied feature selection, subsequent experimental validation MPTP-induced mouse models. Single-cell transcriptomic profiling molecular docking studies performed map target expression assess drug-target interactions. Result A total 1615 DEGs 200 WGCNA obtained, the ORGs DRGs resulted 202 DEORGs, 11 DEDRGs, 5 DED-ORGs (NDUFS2, LRPPRC, NDUFS1, GLUD1, MYH6). are mainly associated stress, respiratory electron transport chain, ATP metabolic process, phosphorylation, mitochondrial respiration, TCA cycle. 10 have good value, including dataset (AUC ≥ 0.507). yielded 6 genes, ACO2, CYCS, HSPA9, SNCA, SDHA, VDAC1. In mice model, SDHA decreased while VDAC1 increased, decreased. Additionally, it discovered that N-Acetylcysteine (NAC) could inhibit occurrence disulfidptosis model. Subsequently, distribution AUC > 0.7 different types brain analyzed. Finally, between anti-PD drugs entering clinical phase IV genes. LRPPRC low binding energy strong affinity duloxetine donepezil, energies -7.6 kcal/mol − 8.7 kcal/mol, respectively. Conclusion This study elucidates pathogenic role OS-induced progression. By identifying biomarkers (e.g., DED-ORGs) therapeutic targets LRPPRC), our findings provide mechanistic framework management lay groundwork future development.

Язык: Английский

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The Genetic Landscape of Sleep Disorders in Parkinson’s Disease

Diagnostics, Год журнала: 2024, Номер 14(1), С. 106 - 106

Опубликована: Янв. 3, 2024

Parknson’s disease (PD) is the second most common neurodegenerative disease, affecting 1% of people aged over 60. PD characterized by a wide range motor symptoms, however clinical spectrum covers non-motor as well. Sleep disorders are among symptoms PD, can occur at any stage and significantly affect quality life. These include rapid eye movement sleep behavior disorder (RBD), restless legs syndrome (RLS), excessive daytime sleepiness (EDS), insomnia, obstructive apnea (OSA) circadian rhythm disturbances. One main challenges in research identifying individuals during prodromal phase disease. Combining genetic data may aid early identification susceptible to PD. This review highlights current regarding component patients, focusing on genes that have currently been associated with this co-morbidity.

Язык: Английский

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Mild cognitive impairment in Parkinson's disease: current view

Frontiers in Cognition, Год журнала: 2024, Номер 3

Опубликована: Апрель 5, 2024

Parkinson's disease (PD), the most common motor movement disorder and second neurodegenerative after Alzheimer's (AD), is often preceded by a period of mild cognitive impairment (MCI), which associated with variety domains including executive function, attention, visuospatial abilities memory. MCI, risk factor for developing dementia, affects around 30% de novo PD patients can increase to 75% more than 10 years. While 30–40% remain in MCI state, up 60% will convert dementia. Characteristic findings are slowing EEG rhythms, frontotemporal hypoperfusion, decreased functional connectivity default mode attentional networks, prefrontal basal-ganglia-cortical circuits, manifests prior clinical symptoms overt brain atrophy. The heterogeneity phenotypes suggests that process multiple neuronal networks neuromodulatory systems may be superimposed Lewy body Alzheimer's-related or other co-pathologies. Sparse neuropathological data PD-MCI revealed heterogenous picture various morphological changes similar diseases. This review highlights essential epidemiological, clinical, neuroimaging PD-MCI, available biomarkers, discusses pathobiological mechanisms involved its development. In view complex pathogenesis, well-designed longitudinal clinico-pathological studies warranted clarify alterations leading PD, supported fluid biomarkers as basis early diagnosis future adequate treatment modalities this debilitating disorder.

Язык: Английский

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Soot nanoparticles promote ferroptosis in dopaminergic neurons via alteration of m6A RNA methylation in Parkinson’s disease

Journal of Hazardous Materials, Год журнала: 2024, Номер 473, С. 134691 - 134691

Опубликована: Май 22, 2024

Язык: Английский

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