Idebenone Protects Photoreceptors Impaired by Oxidative Phosphorylation Disorder in Retinal Detachment DOI Creative Commons
Li‐Song Wang,

Gaocheng Zou,

Yuanye Yan

et al.

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(1), P. 17 - 17

Published: Jan. 8, 2025

Purpose: Oxidative phosphorylation (OXPHOS) is an aerobic metabolic mechanism, and its dysfunction plays important role in the pathological changes of ischemic diseases. However, systematic studies on occurrence retinal detachment (RD) are lacking. Methods: Single-cell RNA sequencing (scRNA-seq) human retina was performed to detect various cells after RD. In this study, animal experiments were conducted explore OXPHOS activity addition, idebenone, a coenzyme Q10 (CoQ10) analog currently used treat Leber hereditary optic neuropathy (LHON), improve disorder experimental RD model. Results: ScRNA-seq revealed abnormal energy metabolism pathways Adenosine triphosphate (ATP) reactive oxygen species (ROS) main products OXPHOS, mouse model indicated that rise ROS levels may have greater impact photoreceptors early stage, whereas decreased ATP synthesis observed later stage; these threaten function morphology retina. Idebenone administered mice intragastrically, leading reduced stage post-RD improved which closely related maintenance mitochondrial morphology. Conclusions: leads photoreceptor degeneration RD, can be alleviated by improving function.

Language: Английский

Effect of the ROCK inhibitor fasudil on the brain proteomic profile in the tau transgenic mouse model of Alzheimer's disease DOI Creative Commons
Roberto Collu, Zheng Yin, Elisa Giunti

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Feb. 19, 2024

Introduction The goal of this study is to explore the pharmacological potential amyloid-reducing vasodilator fasudil, a selective Ras homolog (Rho)-associated kinases (ROCK) inhibitor, in P301S tau transgenic mouse model (Line PS19) neurodegenerative tauopathy and Alzheimer's disease (AD). Methods We used LC-MS/MS, ELISA bioinformatic approaches investigate effect treatment with fasudil on brain proteomic profile PS19 mice. also explored efficacy reducing phosphorylation, beneficial and/or toxic effects its administration Results Proteomic profiling mice brains exposed revealed activation mitochondrial tricarboxylic acid (TCA) cycle blood-brain barrier (BBB) gap junction metabolic pathways. observed significant negative correlation between levels phosphorylated (pTau) at residue 396 both metabolite hydroxyfasudil. Conclusions Our results provide evidence proteins pathways related mitochondria BBB functions by support further development therapeutic for AD.

Language: Английский

Citations

10
Pyridoxal-5-phosphate mitigates age-related metabolic imbalances in the rat heart through the H2S/AKT/GSK3β signaling axis DOI
N.А. Strutynska, Volodymyr V. Balatskyi, Ruslan B. Strutynskyi

et al.

Mitochondrion, Journal Year: 2025, Volume and Issue: unknown, P. 102001 - 102001

Published: Jan. 1, 2025

Language: Английский

Citations

1
Silibinin’s role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer’s disease models DOI
Baohui Zhang, Di Zhang, Keyan Chen

et al.

APOPTOSIS, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 20, 2025

Language: Английский

Citations

1
Reverse Electron Transport at Mitochondrial Complex I in Ischemic Stroke, Aging, and Age-Related Diseases DOI Creative Commons
Vishal Chavda, Bingwei Lu

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 895 - 895

Published: April 6, 2023

Stroke is one of the leading causes morbidity and mortality worldwide. A main cause brain damage by stroke ischemia-reperfusion (IR) injury due to increased production reactive oxygen species (ROS) energy failure caused changes in mitochondrial metabolism. Ischemia a build-up succinate tissues NADH: ubiquinone oxidoreductase (complex I) activity that promote reverse electron transfer (RET), which portion electrons derived from are redirected ubiquinol along complex I reach NADH dehydrogenase module I, where matrix NAD+ converted excessive ROS produced. RET has been shown play role macrophage activation response bacterial infection, transport chain reorganization supply, carotid body adaptation levels. In addition stroke, deregulated RET-generated (RET-ROS) have implicated tissue during organ transplantation, whereas an RET-induced NAD+/NADH ratio decrease aging, age-related neurodegeneration, cancer. this review, we provide historical account roles oxidative pathogenesis ischemic summarize latest developments our understanding biology RET-associated pathological conditions, discuss new ways target cancer, neurodegenerative diseases modulating RET.

Language: Английский

Citations

21
Mitochondrial Dysfunction as a Signaling Target for Therapeutic Intervention in Major Neurodegenerative Disease DOI
Shubhada Mangrulkar, Nitu L. Wankhede, Mayur B. Kale

et al.

Neurotoxicity Research, Journal Year: 2023, Volume and Issue: 41(6), P. 708 - 729

Published: May 10, 2023

Language: Английский

Citations

20
Mitochondrial Modulators: The Defender DOI Creative Commons
Emmanuel Ayobami Makinde, Linlin Ma, George D. Mellick

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(2), P. 226 - 226

Published: Jan. 24, 2023

Mitochondria are widely considered the "power hub" of cell because their pivotal roles in energy metabolism and oxidative phosphorylation. However, beyond production ATP, which is major source chemical supply eukaryotes, mitochondria also central to calcium homeostasis, reactive oxygen species (ROS) balance, apoptosis. The perform crucial multifaceted biosynthetic pathways, serving as an important building blocks for biosynthesis fatty acid, cholesterol, amino glucose, heme. Since play multiple vital cell, it not surprising that disruption mitochondrial function has been linked a myriad diseases, including neurodegenerative cancer, metabolic disorders. In this review, we discuss key physiological pathological functions present bioactive compounds with protective effects on mechanisms action. We highlight promising existing difficulties limiting therapeutic use these potential solutions. provide insights perspectives into future research windows modulators.

Language: Английский

Citations

17
Anthocyanins from blueberry ameliorated arsenic-induced memory impairment, oxidative stress, and mitochondrial-biosynthesis imbalance in rat hippocampal neurons DOI
Xinbo Ma, Yang Liu, Bo Ding

et al.

Cellular Signalling, Journal Year: 2024, Volume and Issue: 119, P. 111177 - 111177

Published: April 15, 2024

Language: Английский

Citations

7
Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes DOI Open Access
Hiroshi Kobayashi,

Shogo Imanaka

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 13144 - 13144

Published: Dec. 6, 2024

The efficacy of assisted reproductive technologies (ARTs) in older women remains constrained, largely due to an incomplete understanding the underlying pathophysiology. This review aims consolidate current knowledge on age-associated mitochondrial alterations and their implications for ovarian aging, with emphasis causes DNA (mtDNA) mutations, repair mechanisms, future therapeutic directions. Relevant articles published up 30 September 2024 were identified through a systematic search electronic databases. free radical theory proposes that reactive oxygen species (ROS) inflict damage mtDNA impair function essential ATP generation oocytes. Oocytes face prolonged pressure persisting five decades. MtDNA exhibits limited capacity double-strand break repair, heavily depending poly ADP-ribose polymerase 1 (PARP1)-mediated single-strand breaks. process depletes nicotinamide adenine dinucleotide (NAD⁺) ATP, creating detrimental cycle where continued further compromises oocyte functionality. Interventions interrupt this destructive may offer preventive benefits. In conclusion, cumulative burden mutations demands can lead depletion elevate risk aneuploidy, ultimately contributing ART failure women.

Language: Английский

Citations

7
The involvement of the mitochondrial membrane in drug delivery DOI Open Access
Yinghui Huang, Wenhui Ji, Jiaxin Zhang

et al.

Acta Biomaterialia, Journal Year: 2024, Volume and Issue: 176, P. 28 - 50

Published: Jan. 26, 2024

Language: Английский

Citations

6
Therapeutic Potential of Targeting Mitochondria for Alzheimer’s Disease Treatment DOI Open Access
Anna Atlante, Giuseppina Amadoro, Valentina Latina

et al.

Journal of Clinical Medicine, Journal Year: 2022, Volume and Issue: 11(22), P. 6742 - 6742

Published: Nov. 14, 2022

Alzheimer's disease (AD), a chronic and progressive neurodegenerative disease, is characterized by memory cognitive impairment the accumulation in brain of abnormal proteins, more precisely beta-amyloid (β-amyloid or Aβ) Tau proteins. Studies aimed at researching pharmacological treatments against AD have focused on molecules capable, one way another, preventing/eliminating accumulations aforementioned Unfortunately, than 100 years after discovery there still no effective therapy modifying biology behind nipping bud. This state affairs has made neuroscientists suspicious, so much that for several idea gained ground not direct neuropathological consequence taking place downstream deposition two toxic but rather multifactorial including mitochondrial dysfunction as an early event pathogenesis AD, occurring even before clinical symptoms. reason why search agents capable normalizing functioning these subcellular organelles vital importance nerve cells certainly to be considered promising approach design neuroprotective drugs preserving this organelle arrest delay progression disease. Here, our intent provide updated overview alterations related disorder therapeutic strategies (both natural synthetic) targeting dysfunction.

Language: Английский

Citations

23