Mitochondrial dysfunction in Parkinson’s disease – a key disease hallmark with therapeutic potential

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Ноя. 11, 2023

Abstract Mitochondrial dysfunction is strongly implicated in the etiology of idiopathic and genetic Parkinson’s disease (PD). However, strategies aimed at ameliorating mitochondrial dysfunction, including antioxidants, antidiabetic drugs, iron chelators, have failed disease-modification clinical trials. In this review, we summarize cellular determinants impairment electron transport chain complex 1, increased oxidative stress, disturbed quality control mechanisms, bioenergetic deficiency. addition, outline pathways to neurodegeneration current context PD pathogenesis, review past treatment an attempt better understand why translational efforts thus far been unsuccessful.

Язык: Английский

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An Epigenetic Role of Mitochondria in Cancer

Cells, Год журнала: 2022, Номер 11(16), С. 2518 - 2518

Опубликована: Авг. 13, 2022

Mitochondria are not only the main energy supplier but also cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which substrates for DNA methylation histone post-translation modifications, essential gene transcriptional regulation fate determination. Tumorigenesis is attributed to many factors, including mutations tumor microenvironment. initiation, evolution, metastasis, recurrence. Targeting mitochondrial metabolism promising therapeutic strategies treatment. In this review, we summarize of mitochondria required modification discuss current strategy cancer therapies via targeting epigenetic modifiers related enzymes This review an important contribution understanding metabolic-epigenetic-tumorigenesis concept.

Язык: Английский

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Nanocatalytic Biofunctional MOF Coating on Titanium Implants Promotes Osteoporotic Bone Regeneration through Cooperative Pro-osteoblastogenesis MSC Reprogramming

ACS Nano, Год журнала: 2022, Номер 16(9), С. 15397 - 15412

Опубликована: Сен. 15, 2022

An elevated bone microenvironmental reactive oxygen species (ROS) level is a hallmark of osteoporosis that often leads to the dysfunction bone-related mesenchymal stem cells (MSCs), which would induce MSC senescence and severely undermine their osteoblastic potential. Herein, we report in situ construction microenvironment-responsive biofunctional metal-organic framework (bio-MOF) coating on titanium surface through coordination between p-xylylenebisphosphonate (PXBP) Ce/Sr ions by hydrothermal method. Taking advantage anchored Ce Sr ions, AHT-Ce/SrMOF implants demonstrate on-demand superoxide dismutase catalase-like catalytic activities decompose ROS MSCs restore mitochondrial functions. In vitro analysis showed substantially activated AMP-activated protein kinase (AMPK) signaling pathway reduced levels. Meanwhile, grown displayed significantly higher expressions fission marker (DRP1), fusion (MFN2 OPA1), mitophagy (PINK1 LC3) than those AHT-CeMOF AHT-SrMOF groups, indicated bio-MOF could amend function reverse senescence. vivo evaluations bio-MOF-coated Ti implant site promote new formation, leading improved osteointegration osteoporotic rat. This study may improve implant-mediated fracture healing clinics.

Язык: Английский

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Numb/Parkin-directed mitochondrial fitness governs cancer cell fate via metabolic regulation of histone lactylation

Cell Reports, Год журнала: 2023, Номер 42(2), С. 112033 - 112033

Опубликована: Янв. 31, 2023

Cell plasticity and neuroendocrine differentiation in prostate lung adenocarcinomas are one of the major reasons for therapeutic resistance to targeted therapy. Whether how metabolic changes contribute this adenocarcinoma-to-neuroendocrine cell fate transition remains largely unclear. Here we show that or cancer cells possess mostly fragmented mitochondria with low membrane potential rely on glycolysis energy metabolism. We further an important role determinant Numb mitochondrial quality control via binding Parkin facilitating Parkin-mediated mitophagy. Deficiency Numb/Parkin pathway causes a reprogramming featured significant increase production lactate acid, which subsequently leads upregulation histone lactylation transcription neuroendocrine-associated genes. Collectively, Numb/Parkin-directed fitness is key switch promising target through regulation lactylation.

Язык: Английский

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Next Generation Gold Drugs and Probes: Chemistry and Biomedical Applications

Chemical Reviews, Год журнала: 2023, Номер 123(10), С. 6612 - 6667

Опубликована: Апрель 18, 2023

The gold drugs, sodium thiomalate (Myocrisin), aurothioglucose (Solganal), and the orally administered auranofin (Ridaura), are utilized in modern medicine for treatment of inflammatory arthritis including rheumatoid juvenile arthritis; however, new agents have been slow to enter clinic. Repurposing different disease indications such as cancer, parasitic, microbial infections clinic has provided impetus development complexes biomedical applications based on unique mechanistic insights differentiated from auranofin. Various chemical methods preparation physiologically stable associated mechanisms explored biomedicine therapeutics or probes. In this Review, we discuss chemistry next generation which encompasses oxidation states, geometry, ligands, coordination, organometallic compounds infectious diseases, inflammation, tools biology via gold-protein interactions. We will focus within past decade. Review provides readers with an accessible overview utility, development, mechanism action gold-based small molecules establish context basis thriving resurgence medicine.

Язык: Английский

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Molecular mechanisms of aging and anti-aging strategies

Cell Communication and Signaling, Год журнала: 2024, Номер 22(1)

Опубликована: Май 24, 2024

Abstract Aging is a complex and multifaceted process involving variety of interrelated molecular mechanisms cellular systems. Phenotypically, the biological aging accompanied by gradual loss function systemic deterioration multiple tissues, resulting in susceptibility to aging-related diseases. Emerging evidence suggests that closely associated with telomere attrition, DNA damage, mitochondrial dysfunction, nicotinamide adenine dinucleotide levels, impaired macro-autophagy, stem cell exhaustion, inflammation, protein balance, deregulated nutrient sensing, altered intercellular communication, dysbiosis. These age-related changes may be alleviated intervention strategies, such as calorie restriction, improved sleep quality, enhanced physical activity, targeted longevity genes. In this review, we summarise key historical progress exploration important causes anti-aging strategies recent decades, which provides basis for further understanding reversibility phenotypes, application prospect synthetic biotechnology therapy also prospected.

Язык: Английский

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FOXO transcription factors as mediators of stress adaptation

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 25(1), С. 46 - 64

Опубликована: Сен. 14, 2023

Язык: Английский

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Mitochondrial pores at the crossroad between cell death and inflammatory signaling

Molecular Cell, Год журнала: 2023, Номер 83(6), С. 843 - 856

Опубликована: Март 1, 2023

Язык: Английский

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Metabolic regulation of the hallmarks of stem cell biology

Cell stem cell, Год журнала: 2024, Номер 31(2), С. 161 - 180

Опубликована: Фев. 1, 2024

Язык: Английский

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A novel protein CYTB-187AA encoded by the mitochondrial gene CYTB modulates mammalian early development

Cell Metabolism, Год журнала: 2024, Номер 36(7), С. 1586 - 1597.e7

Опубликована: Май 3, 2024

Язык: Английский

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