Nrf2-Keap1 signaling in oxidative and reductive stress

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2018, Volume and Issue: 1865(5), P. 721 - 733

Published: Feb. 27, 2018

Language: Английский

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Mitophagy inhibits amyloid-β and tau pathology and reverses cognitive deficits in models of Alzheimer’s disease

Nature Neuroscience, Journal Year: 2019, Volume and Issue: 22(3), P. 401 - 412

Published: Feb. 11, 2019

Language: Английский

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Autophagy in healthy aging and disease

Nature Aging, Journal Year: 2021, Volume and Issue: 1(8), P. 634 - 650

Published: Aug. 12, 2021

Language: Английский

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Mitochondrial and metabolic dysfunction in ageing and age-related diseases

Nature Reviews Endocrinology, Journal Year: 2022, Volume and Issue: 18(4), P. 243 - 258

Published: Feb. 10, 2022

Language: Английский

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Regulation of Mitochondrial Biogenesis as a Way for Active Longevity: Interaction Between the Nrf2 and PGC-1α Signaling Pathways

Frontiers in Genetics, Journal Year: 2019, Volume and Issue: 10

Published: May 14, 2019

Aging is a general degenerative process related to deterioration of cell functions in the entire organism. Mitochondria, which play key role energy homeostasis and metabolism reactive oxygen species (ROS), require lifetime control constant renewal. This explains recently peaked interest processes mitochondrial biogenesis mitophagy. The principal event regulation DNA (mtDNA) transcription translation, complex coordinated that involves at least two systems factors. It commonly believed its major regulatory protein PGC-1α, acts as factor connecting several regulator cascades involved metabolism. In recent years, number publications on essential Nrf2/ARE signaling has grown exponentially. Nrf2 induced by various xenobiotics antioxidants oxidize some negative regulators. Thus, ROS, particular H2O2, were found be strong activators. At present, there are concepts biogenesis. Some authors suggest direct involvement this process. Others believe regulates expression antioxidant genes, while only PGC-1α. Several studies have demonstrated existence loop involving both PGC-1α Nrf2. review, we summarized data mutual promising targets for drug application other therapies aimed increase active longevity.

Language: Английский

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Cell Biology of the Mitochondrion

Genetics, Journal Year: 2017, Volume and Issue: 207(3), P. 843 - 871

Published: Oct. 25, 2017

Abstract Mitochondria are best known for harboring pathways involved in ATP synthesis through the tricarboxylic acid cycle and oxidative phosphorylation. Major advances understanding these roles were made with Caenorhabditiselegans mutants affecting key components of metabolic pathways. These have not only helped elucidate some intricacies metabolism pathways, but they also served as jumping off points pharmacology, toxicology, aging studies. The field mitochondria research has undergone a renaissance, increased appreciation role cell processes other than energy production. Here, we focus on discoveries that using C. elegans, few excursions into areas studied more thoroughly organisms, like mitochondrial protein import yeast. Advances biogenesis membrane dynamics novel functions fission fusion proteins. Some apparent use diverse model systems, such elegans. Studies stress responses, exemplified by mitophagy unfolded response, benefitted greatly from organisms. Recent developments include elegans autonomous nonautonomous controlling well mechanisms degradation paternal after fertilization. evolutionary conservation many, if all, ensures results obtained equally applicable to studies human health disease.

Language: Английский

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Mitophagy: An Emerging Role in Aging and Age-Associated Diseases

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: March 26, 2020

Mitochondrial dysfunction constitutes one of the hallmarks aging and is characterized by irregular mitochondrial morphology, insufficient ATP production, accumulation DNA (mtDNA) mutations, increased production reactive oxygen species (ROS) consequent oxidative damage to nucleic acids, proteins lipids. Mitophagy, a quality control mechanism enabling degradation damaged superfluous mitochondria, prevents such detrimental effects reinstates cellular homeostasis in response stress. To date, there increasing evidence that mitophagy significantly impaired several human pathologies including age-related diseases as neurodegenerative disorders, cardiovascular cancer. Therapeutic interventions aiming at induction may have potency ameliorate these dysfunctions. In this review, we summarize recent findings on mechanisms controlling its role development pathologies.

Language: Английский

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NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Nov. 21, 2019

Abstract Metabolic dysfunction is a primary feature of Werner syndrome (WS), human premature aging disease caused by mutations in the gene encoding (WRN) DNA helicase. WS patients exhibit severe metabolic phenotypes, but underlying mechanisms are not understood, and whether deficit can be targeted for therapeutic intervention has been determined. Here we report impaired mitophagy depletion NAD + , fundamental ubiquitous molecule, patient samples invertebrate models. WRN regulates transcription key biosynthetic enzyme nicotinamide nucleotide adenylyltransferase 1 (NMNAT1). repletion restores profiles improves mitochondrial quality through DCT-1 ULK-1-dependent mitophagy. At organismal level, remarkably extends lifespan delays accelerated aging, including stem cell dysfunction, Caenorhabditis elegans Drosophila melanogaster models WS. Our findings suggest that mediated function mitophagy, bolstering cellular levels counteracts phenotypes.

Language: Английский

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Amelioration of Alzheimer’s disease pathology by mitophagy inducers identified via machine learning and a cross-species workflow

Nature Biomedical Engineering, Journal Year: 2022, Volume and Issue: 6(1), P. 76 - 93

Published: Jan. 6, 2022

Abstract A reduced removal of dysfunctional mitochondria is common to aging and age-related neurodegenerative pathologies such as Alzheimer’s disease (AD). Strategies for treating impaired mitophagy would benefit from the identification modulators. Here we report combined use unsupervised machine learning (involving vector representations molecular structures, pharmacophore fingerprinting conformer fingerprinting) a cross-species approach screening experimental validation new mitophagy-inducing compounds. From library naturally occurring compounds, workflow allowed us identify 18 small molecules, among them two potent inducers (Kaempferol Rhapontigenin). In nematode rodent models AD, show that both increased survival functionality glutamatergic cholinergic neurons, abrogated amyloid-β tau pathologies, improved animals’ memory. Our findings suggest existence conserved mechanism memory loss across AD models, this being mediated by defective mitophagy. The computational–experimental might help uncover modulators stimulate neuronal health brain homeostasis.

Language: Английский

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Mitophagy in human health, ageing and disease

Nature Metabolism, Journal Year: 2023, Volume and Issue: 5(12), P. 2047 - 2061

Published: Nov. 30, 2023

Language: Английский

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