Altered Mitochondrial Morphology and Bioenergetics in a New Yeast Model Expressing Aβ42

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(2), С. 900 - 900

Опубликована: Янв. 4, 2023

Alzheimer's disease (AD) is an incurable, age-related neurological disorder, the most common form of dementia. Considering that AD a multifactorial complex disease, simplified experimental models are required for its analysis. For this purpose, genetically modified Yarrowia lipolytica yeast strains expressing Aβ42 (the main biomarker AD), eGFP-Aβ42, Aβ40, and eGFP-Aβ40 were constructed examined. In contrast to cells eGFP eGFP-Aβ40, retaining "normal" mitochondrial reticulum, eGFP-Aβ42 possessed disturbed reticulum with fragmented mitochondria; was partially restored by preincubation mitochondria-targeted antioxidant SkQThy. expression also elevated ROS production cell death; low concentrations SkQThy mitigated these effects. caused dysfunction as inferred from loose coupling respiration phosphorylation, decreased level ATP production, enhanced rate hydrogen peroxide formation. Therefore, we have obtained same results described other models. Based on analysis earlier data, suggest fragmentation might be earliest preclinical stage effective therapy based mitochondria- targeted antioxidants. The simple model can useful platform rapid screening such compounds.

Язык: Английский

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The immunometabolic reprogramming of microglia in Alzheimerʼs disease

Neurochemistry International, Год журнала: 2023, Номер 171, С. 105614 - 105614

Опубликована: Сен. 23, 2023

Язык: Английский

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Mitochondrial dysfunction and oxidative stress in Alzheimer's disease–A step towards mitochondria based therapeutic strategies

Aging and Health Research, Год журнала: 2023, Номер 3(4), С. 100169 - 100169

Опубликована: Ноя. 8, 2023

Alzheimer's disease (AD) is a neurodegenerative with reduced cognitive function due to mitochondrial dysfunction and oxidative stress. Recent studies show that the pathophysiology of AD may be influenced by dysfunctionality, Ca2+ imbalance, apoptosis, decreased energy, alteration in its metabolism. Study indicates damaged mitochondria play critical roles pathogenesis AD, even if precise mechanism behind remains unknown. It thought healthy pool protects neurons reducing damage caused also promotes neuronal activity giving enough energy other associated functions. In this sense, investigation mechanisms altered constitutes novel, promising therapeutic targets for disease. Mitochondria enhances generation, antioxidants scavenge reactive oxygen species reduce substrate supply, glucose metabolism, potential drug candidates target apoptotic mitophagy pathways remove mitochondria. Although therapy approaches have shown promise preclinical studies, there hasn't been much advancement clinical trials thus far. Therefore, we try find out role highlight development compounds as AD.

Язык: Английский

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Bioinformatics insights into mitochondrial and immune gene regulation in Alzheimer's disease

European journal of medical research, Год журнала: 2025, Номер 30(1)

Опубликована: Фев. 8, 2025

There is growing evidence that the pathogenesis of Alzheimer's disease closely linked to resident innate immune cells central nervous system, including microglia and astrocytes. Mitochondrial dysfunction in has also been reported play an essential role AD other neurological diseases. Therefore, finding mitochondrial immune-related gene (MIRG) signatures can be significant diagnosing treating AD. In this study, intersection differentially expressed genes (DEGs) from GSE109887 cohort, (IRGs) obtained WGCNA analysis, mitochondria-related (MRGs) was taken identify mitochondria-immune-related (MIRGs). Then, using machine learning algorithms, biomarkers with good diagnostic value were selected, a nomogram constructed. Subsequently, we further analyzed signaling pathways potential biological mechanisms through set enrichment prediction transcription factors (TFs), miRNAs, drug prediction. Using five (TSPO, HIGD1A, NDUFAB1, NT5DC3, MRPS30) successfully identified, model strong ability accuracy (AUC > 0.9) addition, single-gene analysis revealed NDUFAB1 significantly enriched associated diseases, such as Parkinson's, providing valuable insights for future clinical research on context mitochondrial-immune interactions. Interestingly, brain tissue pathology showed neuronal atrophy demyelination mice, along reduction Nissl bodies. Furthermore, escape latency mice longer than control group. After platform removal, there notable increase path complexity time required reach target quadrant, suggesting spatial memory capacity mice. Moreover, qRT-PCR validation confirmed mRNA expression consistent bioinformatics results. TSPO increased, while MRPS30 expressions decreased. However, peripheral blood samples did not show HIGD1A or MRPS30. These findings provide new interactions, exploring offering perspectives development novel drugs. Five biomarkers, i.e., TSPO, MRPS30, disease, screened by machine-learning algorithmic models, which will guide mitochondria-immunity-related direction.

Язык: Английский

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Voluntary wheel exercise improves learning and memory impairment caused by hippocampal Hb-α deficiency by reducing microglial activation and reversing synaptic damage

Brain Behavior and Immunity, Год журнала: 2025, Номер 127, С. 81 - 95

Опубликована: Март 7, 2025

Язык: Английский

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