Mitochondrial dysfunction in Alzheimer's disease: Guiding the path to targeted therapies

Neurotherapeutics, Год журнала: 2025, Номер unknown, С. e00525 - e00525

Опубликована: Янв. 1, 2025

Язык: Английский

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Altered Mitochondrial Function in MASLD: Key Features and Promising Therapeutic Approaches

Antioxidants, Год журнала: 2024, Номер 13(8), С. 906 - 906

Опубликована: Июль 26, 2024

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty (NAFLD), encompasses a range of conditions from steatosis to steatohepatitis (NASH). Its prevalence, especially among patients with metabolic syndrome, highlights its growing global impact. The pathogenesis MASLD involves dysregulation, inflammation, oxidative stress, genetic factors and, notably, mitochondrial dysfunction. Recent studies underscore the critical role dysfunction in MASLD's progression. Therapeutically, enhancing function has gained interest, along lifestyle changes and pharmacological interventions targeting processes. FDA's approval resmetirom for metabolic-associated (MASH) fibrosis marks significant step. While represents progress, further research is essential understand MASLD-related fully. Innovative strategies like gene editing small-molecule modulators, alongside interventions, can potentially improve treatment. Drug repurposing new targets will advance therapy, addressing increasing burden. Therefore, this review aims provide better understanding identify more effective preventive treatment strategies.

Язык: Английский

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Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease

Antioxidants, Год журнала: 2023, Номер 12(4), С. 973 - 973

Опубликована: Апрель 21, 2023

Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging cellular senescence. Evidence suggests that oxidative damage not solely due exogenous exposure inhaled irritants, but also endogenous sources oxidants in the form reactive oxygen species (ROS). Mitochondria, producers ROS, exhibit impaired structure function resulting reduced capacity excessive ROS production. Antioxidants have been shown protect against ROS-induced by reducing levels, inflammation, protecting development emphysema. However, currently available antioxidants are routinely used management suggesting need for more effective antioxidant agents. In recent years, number mitochondria-targeted (MTA) compounds developed capable crossing mitochondria lipid bilayer, offering targeted approach at its source. particular, MTAs illicit greater protective effects compared non-targeted, further apoptosis protection mtDNA they promising therapeutic agents treatment COPD. Here, we review evidence potential as chronic disease discuss current challenges future directions.

Язык: Английский

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Mitochondrial transplantation combined with mitoquinone and melatonin: A survival strategy against myocardial reperfusion injury in aged rats

Experimental Physiology, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Abstract Myocardial ischaemia–reperfusion (IR) injury poses a severe threat to cardiac health, particularly in the ageing population, where susceptibility such damage is significantly heightened owing age‐related declines mitochondrial function, thus highlighting mitochondria as crucial targets for innovative therapies. The aim of this study was investigate combined modality therapy involving transplantation and boosters mitoquinone melatonin address myocardial IR aged rats. A total 54 male Wistar rats, 22–24 months, were randomly divided into groups that either received or not, subjected various treatments, both individually combination. induced by temporarily blocking reopening left anterior descending coronary artery. Mitoquinone given intraperitoneally 14 days prior ischaemia, while isolated administered intramyocardially, respectively, at onset reperfusion. Finally, we evaluated changes haemodynamic indices, creatine kinase‐MB levels, function endpoints expression biogenesis genes, including sirtuin 1 ( SIRT‐1 ), peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha PGC‐1α ) nuclear respiratory factor 2 NRF‐2 ). triple enhanced decreased levels improved along with genes This approach elicited significant cardioprotection comparison single dual provided substantial rat hearts improving through / profiles, suggesting promising strategy mitigating elderly patients.

Язык: Английский

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Mitochondrial Chronic Progressive External Ophthalmoplegia

Brain Sciences, Год журнала: 2024, Номер 14(2), С. 135 - 135

Опубликована: Янв. 27, 2024

Background: Chronic progressive external ophthalmoplegia (CPEO) is a rare disorder that can be at the forefront of several mitochondrial diseases. This review overviews CPEO encephalomyopathies to enhance accurate recognition and diagnosis for proper management. Methods: study conducted based on publications guidelines obtained by selective in PubMed. Randomized, double-blind, placebo-controlled trials, Cochrane reviews, literature meta-analyses were particularly sought. Discussion: common presentation encephalomyopathies, which result from alterations or nuclear DNA. Genetic sequencing gold standard diagnosing preceded non-invasive tests such as fibroblast growth factor-21 differentiation factor-15. More invasive options include muscle biopsy, carried out after uncertain diagnostic testing. No definitive treatment option available diseases, management mainly focused lifestyle risk modification supplementation reduce load symptomatic relief, ptosis repair case CPEO. Nevertheless, various clinical trials endeavors are still large achieving beneficial therapeutic outcomes encephalomyopathies. Key Messages: Understanding varying presentations genetic aspects crucial

Язык: Английский

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Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight

Pathophysiology, Год журнала: 2025, Номер 32(1), С. 9 - 9

Опубликована: Фев. 13, 2025

Diabetes mellitus represents a complicated metabolic condition marked by ongoing hyperglycemia arising from impaired insulin secretion, inadequate action, or combination of both. Mitochondrial dysfunction has emerged as significant contributor to the aetiology diabetes, affecting various processes critical for glucose homeostasis. This review aims elucidate complex link between mitochondrial and covering spectrum diabetes types, role mitochondria in resistance, highlighting pathophysiological mechanisms, DNA damage, altered biogenesis dynamics. Additionally, it discusses clinical implications complications its complications, diagnostic approaches assessing function diabetics, therapeutic strategies, future directions, research opportunities.

Язык: Английский

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Impact of combined alpha-lipoic acid and mitoquinone supplementation on myocardial infarction in aged rats: Heart performance and molecular mechanisms

Experimental Gerontology, Год журнала: 2024, Номер 189, С. 112402 - 112402

Опубликована: Март 19, 2024

This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function underlying mechanisms in aged rats with myocardial infarction (MI). The underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion 24 h. ALA (100 mg/kg, gavage) Mito Q (10 IP) were administered daily two weeks before ischemia. Cardiac function, inflammatory, apoptotic markers evaluated h after results this indicated that administration combination significantly improved function. improvement was linked a reduction expression pro-inflammatory cytokines TNF-α, IL-6, IL-1β (P < 0.001) (Bax, caspase-3, Cyt-c), as well decrease percentage TUNEL-positive cells 0.001). revealed intervention synergistically mitigated dysfunction suppressing inflammatory pathways MI. Further research is needed validate potential therapeutic options elderly people at risk heart attacks.

Язык: Английский

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Emerging and Novel Therapeutic Treatments Targeting Mitochondrial-Endoplasmic Reticulum Contact Sites in Metabolic and Vascular Disorders

International Journal of Drug Discovery and Pharmacology, Год журнала: 2024, Номер unknown, С. 100008 - 100008

Опубликована: Июнь 6, 2024

Review Emerging and Novel Therapeutic Treatments Targeting Mitochondrial-Endoplasmic Reticulum Contact Sites in Metabolic Vascular Disorders Richard M. Monaghan The British Heart Foundation Centre of Research Excellence Manchester, Division Cardiovascular Sciences, Faculty Biology, Medicine, Health, University AV Hill Building, Oxford Road, M13 9PN, UK;[email protected] Received: 10 April 2024; Revised: 5 May Accepted: 7 Published: 6 June 2024 Abstract: Subcellular organellar contact sites, particularly those between mitochondria the endoplasmic reticulum (MERCSs), play crucial roles maintaining health. These specialized partitions facilitate vital communication organelles, regulating processes essential for cell function, including calcium balance, lipid biogenesis transport, mitochondrial dynamics, programmed death. Growing evidence shows that perturbation MERCSs contributes significantly to various diseases, neurodegenerative disorders like Alzheimer’s Parkinson’s, metabolic issues, such as type 2 diabetes, heart conditions, cancer. This review dives into this expanding field, exploring potential therapeutic targets. It provides a detailed overview proteins form maintain MERCSs, highlighting how their disruption can lead cellular dysfunction disease. Additionally, it examines recent exciting breakthroughs developing drugs strategies manipulate clinical benefits. While challenges remain, emphasises MERCS-based therapies outlines critical research needed move these treatments from lab clinic.

Язык: Английский

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Targeting Hydroxybenzoic Acids to Mitochondria as a Strategy to Delay Skin Ageing: An In Vitro Approach

Molecules, Год журнала: 2022, Номер 27(19), С. 6183 - 6183

Опубликована: Сен. 21, 2022

Targeting antioxidants to mitochondria is considered a promising strategy prevent cellular senescence and skin ageing. In this study, we investigate whether four hydroxybenzoic acid-based mitochondria-targeted (MitoBENs, MB1-4) could be used as potential active ingredients in cells. Firstly, evaluated the chemical stability, cytotoxicity, genotoxicity mitochondrial toxicity of all compounds. We followed by testing antioxidant protective capacity two less toxic compounds on human fibroblasts. then assessed effects best hit senescence, inflammation remodeling 3D cell model, while also its mutagenic potential. Cytotoxicity rankings were produced: MB3 < MB4 ≃ MB1 MB2 MB2, respectively. These results suggest that pyrogallol-based (MB2 MB4) have lower cytotoxicity. The pyrogallol derivative, containing 6-carbon spacer, showed more potent activity against hydrogen peroxide decreased transcripts related senescence. sum, MB2’s biological safety profile, good stability lack mutagenicity, combined with anti-senescence effect, converts into candidate for further development an ingredient anti-ageing products.

Язык: Английский

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Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption

Chronobiology International, Год журнала: 2023, Номер 40(8), С. 1004 - 1027

Опубликована: Авг. 3, 2023

ABSTRACTEnvironmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed evaluate the effects of circadian rhythm disruption on reproductive metabolic functions investigate potential therapeutic benefits MitoQ10 hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, three groups with PCOS induced continuous light exposure(L/L). The reproductive, endocrine, structural manifestations ofL/L-induced confirmed serum biochemical measurements, ultrasound evaluation ovarian size, vaginal smear examination at week 14. Subsequently, L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At end 22, all sacrificed. Treatmentwith HTT partially reversed features PCOS, leading a decreased amplitude isolated uterine contractions, cystic changes endometrial thickness. Furthermore, both interventions improved elevated levels anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin metalloproteinase thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) their transcription target genes, FKBP52 immunostaining in tissues, estrogen receptor alpha (ER-α) PRimmunostaining. In conclusion, supplementation demonstrated ameliorating metabolic, perturbations associated disruption. These findings suggest role these managing women.KEYWORDS: PCOSoxidative stresscircadian rhythmreproductive functionFKBP52Fibulin-1ADAMTS-19 Disclosure statementNo conflict interest was reported author(s).Ethical approvalThis followed guidelines set Institutional Review Board Hashemite University, which approved (15/2020) experimental procedures, animal handling, sampling, euthanasia. Animal handling adhered principles outlined Guide Care Use Laboratory Animals (NIH publication no. 85–23, revised 2011).Data availability statementThe datasets used current are available from corresponding author upon reasonable request.Additional informationFundingThe work supported University [59/2020].

Язык: Английский

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