Intercellular mitochondrial transfer in the brain, a new perspective for targeted treatment of central nervous system diseases

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(11), P. 3121 - 3135

Published: July 9, 2023

Mitochondria is one of the important organelles involved in cell energy metabolism and regulation also play a key regulatory role abnormal processes such as stress, damage, canceration. Recent studies have shown that mitochondria can be transferred between cells different ways participate occurrence development many central nervous system diseases. We aim to review mechanism mitochondrial transfer progress diseases possibility targeted therapy.The PubMed databank, China National Knowledge Infrastructure Wanfang Data were searched identify experiments intracellular transferrin system. The focus on donors, receptors, pathways, drugs transfer.In system, neurons, glial cells, immune tumor each other. Meanwhile, there are types transfer, including tunneling nanotubes, extracellular vesicles, receptor endocytosis, gap junction channels, intercellular contact. A variety stress signals, release damaged mitochondria, DNA, or other products elevation reactive oxygen species, trigger from donor recipient cells. Concurrently, molecular pathways related inhibitors affect transfer.This study reviews phenomenon summarizes corresponding pathways. Finally, we propose treatment methods may used regulate for

Language: Английский

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Biomarkers of mitochondrial dysfunction in autism spectrum disorder: A systematic review and meta-analysis

Neurobiology of Disease, Journal Year: 2024, Volume and Issue: 197, P. 106520 - 106520

Published: May 3, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental affecting 1 in 36 children and associated with physiological abnormalities, most notably mitochondrial dysfunction, at least subset of individuals. This systematic review meta-analysis discovered 204 relevant articles which evaluated biomarkers dysfunction ASD Significant elevations (all p < 0.01) the prevalence lactate (17%), pyruvate (41%), alanine (15%) creatine kinase (9%) were found ASD. Individuals had significant differences moderate to large effect sizes (Cohen's d' ≥ 0.6) compared controls mean pyruvate, lactate-to-pyruvate ratio, ATP, kinase. Some studies abnormal TCA cycle metabolites Thirteen controlled reported DNA (mtDNA) deletions or variations group blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, brain. Meta-analyses (p copy number mtDNA overall ND1, ND4 CytB genes. Four linked specific haplogroups A series subgroup elevated respiration was increased sensitivity mitochondria stressors regression. Lactate, carnitine, acyl-carnitines clinical features such as delays language, social interaction, cognition, motor skills, repetitive behaviors gastrointestinal symptoms, although not all an association. acyl-carnitines, CoQ10, well variants, heteroplasmy, severity. Variability across biomarker primarily due collection processing techniques intrinsic heterogeneity population. Several alterations metabolism mothers neonates who develop Treatments targeting mitochondria, particularly carnitine ubiquinol, appear beneficial The link between common abnormalities individuals including disorders, oxidative stress, immune outlined. subtypes are discussed, one related regression, another microbiome metabolites, acyl-carnitines. Mechanisms linking function prenatal brain development postnatal Given multisystem complexity some ASD, this presents evidence for being central by contributing development, comorbidities diagnostic approach identify From evidence, it clear that many have may need be addressed order achieve optimal outcomes. fact during pregnancy early life eventually provides promise predictive Further improve understanding role better defining subgroups molecular mechanisms driving unique changes those

Language: Английский

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Nature’s magic: how natural products work hand in hand with mitochondria to treat stroke

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Mitochondria, as the energy factories of cells, are involved in a wide range vital activities, including cell differentiation, signal transduction, cycle, and apoptosis, while also regulating growth. However, current pharmacological treatments for stroke challenged by issues such drug resistance side effects, necessitating exploration new therapeutic strategies. This review aims to summarize regulatory effects natural compounds targeting mitochondria on neuronal mitochondrial function metabolism, providing perspectives treatment. Numerous vitro vivo studies have shown that products berberine, ginsenosides, baicalein protect reduce stroke-induced damage through multiple mechanisms. These apoptosis modulating expression mitochondrial-associated apoptotic proteins. They inhibit activation permeability transition pore (mPTP), thereby decreasing ROS production cytochrome C release, which helps preserve function. Additionally, they regulate ferroptosis, fission, promote autophagy trafficking, further enhancing protection. As multi-target chemical agents, offer high efficacy with fewer present promising potential innovative therapies. Future research should investigate effectiveness safety these clinical applications, advancing their development strategy stroke.

Language: Английский

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Mitochondrial mechanisms in the pathogenesis of chronic inflammatory musculoskeletal disorders

Cell & Bioscience, Journal Year: 2024, Volume and Issue: 14(1)

Published: June 8, 2024

Abstract Chronic inflammatory musculoskeletal disorders characterized by prolonged muscle inflammation, resulting in enduring pain and diminished functionality, pose significant challenges for the patients. Emerging scientific evidence points to mitochondrial malfunction as a pivotal factor contributing these ailments. Mitochondria play critical role powering skeletal activity, but context of persistent disruptions their quantity, configuration, performance have been well-documented. Various disturbances, encompassing alterations dynamics (such fission fusion), calcium regulation, oxidative stress, biogenesis, process mitophagy, are believed central progression disorders. Additionally, unfolded protein responses accumulation fatty acids within cells may adversely affect internal milieu, impairing equilibrium functioning. The structural discrepancies between different subsets namely, intramyofibrillar subsarcolemmal mitochondria likely impact metabolic capabilities susceptibility influences. release signals from damaged is known incite responses. Intriguingly, migrasomes extracellular vesicles serve vehicles intercellular transfer mitochondria, aiding removal impaired regulation inflammation. Viral infections implicated inducing stress on mitochondria. Prolonged dysfunction vital organelles sustains harm, irregularities, heightened cytokine release, impeding body’s ability repair tissues. This review provides comprehensive analysis advancements understanding changes intracellular environment, architecture distribution, dynamics, autophagy, cytokines associated with vesicular structures, membranes chronic Strategies targeting key elements regulating quality exhibit promise restoration function, alleviation enhancement overall outcomes. Graphical

Language: Английский

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Human neural stem cells derived from fetal human brain communicate with each other and rescue ischemic neuronal cells through tunneling nanotubes

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(8)

Published: Sept. 1, 2024

Abstract Pre-clinical trials have demonstrated the neuroprotective effects of transplanted human neural stem cells (hNSCs) during post-ischemic phase. However, exact mechanism remains unclear. Tunneling nanotubes (TNTs) are long plasma membrane bridges that physically connect distant cells, enabling intercellular transfer mitochondria and contributing to repair processes. Whether hNSCs communicate through TNTs their role in neuroprotection unknown. In this study, non-immortalized hNSC lines derived from fetal brain tissues were examined explore these possibilities assess potential hNSCs. Using Tau-STED super-resolution confocal microscopy, live cell time-lapse fluorescence electron direct or non-contact homotypic co-cultures, we generate nestin-positive both 3D neurospheres 2D cultures, which they functional mitochondria. Co-culturing with differentiated SH-SY5Y ( d SH-SY5Y) revealed heterotypic allowing mitochondrial SH-SY5Y. To investigate neuroprotection, subjected oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) without co-cultures. Compared normoxia, OGD/R became apoptotic impaired electrical activity. When co-cultured contact hNSCs, enabled SH-SY5Y, rescuing them apoptosis restoring bioelectrical profile toward normoxic This complete did not occur co-culture. summary, our data reveal presence a network containing nestin within demonstrate involvement mediated highlight strong efficacy neuroprotection.

Language: Английский

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Neuroimmunophysiology of the gastrointestinal tract

AJP Gastrointestinal and Liver Physiology, Journal Year: 2024, Volume and Issue: 326(6), P. G712 - G725

Published: April 16, 2024

Gut physiology is the epicenter of a web internal communication systems (i.e., neural, immune, hormonal) mediated by cell-cell contacts, soluble factors, and external influences, such as microbiome, diet, physical environment. Together these provide signals that shape enteric homeostasis and, when they go awry, lead to disease. Faced with seemingly paradoxical tasks nutrient uptake (digestion) retarding pathogen invasion (host defense), gut integrates interactions between variety cells signaling molecules keep host nourished protected from pathogens. When system fails, outcome can be acute or chronic disease, often labeled "idiopathic" in nature (e.g., irritable bowel syndrome, inflammatory disease). Here we underscore importance holistic approach physiology, placing an emphasis on intercellular connectedness, using neuroimmunophysiology paradigm. The goal this opinion piece acknowledge pace change brought our field via single-cell -omic methodologies other techniques cell lineage tracing, transgenic animal models, methods for culturing patient tissue, advanced imaging. We identify gaps hope inspire challenge colleagues take up mantle advance awareness subtleties, intricacies, nuances intestinal health disease defining pathways resident cells, those recruited circulation, "external" influences central nervous microbiota.

Language: Английский

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Insights into therapeutic approaches for the treatment of neurodegenerative diseases targeting metabolic syndrome

Molecular Biology Reports, Journal Year: 2025, Volume and Issue: 52(1)

Published: Feb. 21, 2025

Language: Английский

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Magnolol protects C6 glioma cells against neurotoxicity of FB1 via modulating PI3K/Akt and mitochondria-associated apoptosis signaling pathways

Environmental Pollution, Journal Year: 2025, Volume and Issue: 372, P. 126017 - 126017

Published: March 6, 2025

Language: Английский

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Osteoblast‐Derived Mitochondria Formulated with Cationic Liposome Guide Mesenchymal Stem Cells into Osteogenic Differentiation

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 31, 2025

Abstract While mitochondria are known to be essential for intracellular energy production and overall function, emerging evidence highlights their role in influencing cell behavior through mitochondrial transfer. This phenomenon provides a potential basis the development of treatment strategies tissue damage degeneration. study aims evaluate whether isolated from osteoblasts can promote osteogenic differentiation mesenchymal stem cells (MSCs). Mitochondria MSCs, which primarily utilize glycolysis, compared with those MG63 cells, depend on oxidative phosphorylation. both types then encapsulated cationic liposomes transferred impact is assessed. delivery MSCs grown two‐ three‐dimensional cultures results increased expression markers, including Runt‐related transcription factor 2, Osterix, Osteopontin, upregulation genes involved Bone morphogenetic protein 2 signaling calcium import. accompanied by influx regulated Wnt/β‐catenin pathway. Transplantation spheroids containing MG63‐derived bone defect animal models improves regeneration. The suggest that effectively guides toward osteogenesis, paving way mitochondria‐transplantation therapies.

Language: Английский

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Isolated Mitochondrial Transplantation as a Novel Treatment for Corneal Chemical Burns

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(3), P. 14 - 14

Published: March 6, 2025

This study aimed to investigate the therapeutic potential of isolated mitochondrial transplantation for restoration corneal surface injury in mice after chemical burn. Mitochondria were from mesenchymal stem cells via ultracentrifugation, followed by an assessment their purity and viability. The internalization mitochondria human epithelial was tracked using a live fluorescence imaging system. Apoptosis-related markers function measured Western blotting flow cytometry, respectively. Mitochondrial morphology examined confocal laser scanning microscopy. effects subconjunctival administration vivo evaluated fluorescein sodium staining histopathological examination corneas. Our demonstrates that possess capacity internalize exogenous vitro. Under oxidative stress conditions, recipient exhibited enhanced uptake mitochondria. We observed decrease apoptosis reduction levels within cells, as well partial function. Notably, single injection, able use enhance repair process mouse model acid Subconjunctival injection promoted acute burns mice. results our investigation treatment modality burn offers novel approach ocular disorders associated with dysfunction.

Language: Английский

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