Mitochondria transfer for myelin repair

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

Demyelination is a common feature of neuroinflammatory and degenerative diseases the central nervous system (CNS), such as multiple sclerosis (MS). It often linked to disruptions in intercellular communication, bioenergetics metabolic balance accompanied by mitochondrial dysfunction cells oligodendrocytes, neurons, astrocytes, microglia. Although current MS treatments focus on immunomodulation, they fail stop or reverse demyelination’s progression. Recent advancements highlight exchange promising therapeutic target, with potential restore homeostasis, enhance promote myelin repair. With this review we will provide insights into CNS decoupling, focusing role demyelinating conditions. We then discuss emerging cell-free biotherapies exploring transferring mitochondria via biogenic carriers like extracellular vesicles (EVs) synthetic liposomes, aimed at enhancing function support for Lastly, address key challenges clinical application these strategies future directions optimize biotherapies. The field hold promise restoring repair, potentially transforming landscape diseases.

Language: Английский

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Mitochondrial quality control and transfer communication in neurological disorders and neuroinflammation

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Mitochondria, as the primary energy factories of cells, play a pivotal role in maintaining nervous system function and regulating inflammatory responses. The balance mitochondrial quality control is critical for neuronal health, disruptions this are often implicated pathogenesis various neurological disorders. Mitochondrial dysfunction not only exacerbates deficits but also triggers neuroinflammation through release damage-associated molecular patterns (DAMPs), such DNA (mtDNA) reactive oxygen species (ROS). This review examines mechanisms recent advancements diseases, focusing on processes fusion fission, mitophagy, biogenesis, protein expression regulation. It further explores subsequent cascades conditions ischemic hemorrhagic stroke, neurodegenerative diseases brain tumors. Additionally, emerging research highlights significance transfer mechanisms, particularly intercellular between neurons glial potential strategy mitigating inflammation promoting cellular repair. provides insights into underpinnings neuroinflammatory pathologies while underscoring translational targeting therapeutic development.

Language: Английский

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Functional mitochondrial respiration is essential for glioblastoma tumour growth

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

Published: May 5, 2025

Abstract Horizontal transfer of mitochondria from the tumour microenvironment to cancer cells support proliferation and enhance progression has been shown for various types in recent years. Glioblastoma, most aggressive adult brain tumour, proven be no exception when it comes dynamic intercellular mitochondrial movement, as this study using an orthotopic model respiration-deficient glioblastoma cells. Although confirmed was facilitate glioblastoma, we decided investigate whether related electron transport chain recovery is necessary formation brain. Based on experiments time-resolved analysis by depleted their DNA, conclude that functional respiration essential growth vivo, because needed coenzyme Q redox cycling de novo pyrimidine biosynthesis controlled respiration-linked dihydroorotate dehydrogenase enzyme activity. We also demonstrate here astrocytes are key donors model.

Language: Английский

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Tunneling Nanotube: An Enticing Cell–Cell Communication in the Nervous System

Biology, Journal Year: 2023, Volume and Issue: 12(10), P. 1288 - 1288

Published: Sept. 27, 2023

The field of neuroscience is rapidly progressing, continuously uncovering new insights and discoveries. Among the areas that have shown immense potential in research, tunneling nanotubes (TNTs) emerged as a promising subject study. These minute structures act conduits for transfer cellular materials between cells, representing mechanism communication holds great significance. In particular, interplay facilitated by TNTs among various cell types within brain, including neurons, astrocytes, oligodendrocytes, glial microglia, can be essential normal development optimal functioning this complex organ. involvement neurodegenerative disorders, such Alzheimer's disease, Huntington's Parkinson's has attracted significant attention. disorders are characterized progressive degeneration neurons subsequent decline brain function. Studies predicted likely play critical roles propagation spread pathological factors, contributing to advancement these diseases. Thus, there growing interest understanding precise functions mechanisms nervous system. This review article, based on our recent work Rhes-mediated TNTs, aims explore investigate their implications Using knowledge gained from studying could offer novel opportunities designing targeted treatments stop progression disorders.

Language: Английский

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Powering prescription: Mitochondria as “Living Drugs” – Definition, clinical applications, and industry advancements

Pharmacological Research, Journal Year: 2023, Volume and Issue: 199, P. 107018 - 107018

Published: Nov. 25, 2023

Mitochondria's role as engines and beacons of metabolism determinants cellular health is being redefined through their therapeutic application "Living Drugs" (LDs). Artificial mitochondrial transfer/transplant (AMT/T), encompassing various techniques to modify, enrich, or restore mitochondria in cells tissues, revolutionizing acellular therapies the future medicine. This article proposes a necessary definition for LDs within Advanced Therapeutic Medicinal Products (ATMPs) framework. While recognizing different types ATMPs, such mesenchymal stem (MSCs) chimeric antigen receptor T (CAR T) cells, we focus on due unique attributes that distinguish them from traditional cell therapies. These include inherent living nature, diverse sources, industry applicability, validation, customizability needs, capability adapt respond recipient cells. We trace journey initial breakthroughs AMT/T current state-of-the-art applications by emerging innovative companies, highlighting need manufacturing standards navigate transition concept clinical practice. By providing comprehensive overview scientific, clinical, commercial landscape LDs, this contributes essential dialogue among regulatory agencies, academia, shape

Language: Английский

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Insomnia in Forensic Detainees: Is Salience Network the Common Pathway for Sleep, Neuropsychiatric, and Neurodegenerative Disorders?

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1691 - 1691

Published: March 15, 2024

Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% hospitalized patients chronic neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect many antipsychotic drugs, further highlighting etiopathogenesis. Since brain salience network likely denominator for insomnia, neurodegenerative here, we focus on pathology this neuronal assembly its driver, dysfunctional mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to transplantation. The aims review are threefold: 1. Examining causes insomnia in forensic detainees illness, as well role predisposing them disorders. 2. Educating State hospital prison clinicians frontotemporal dementia behavioral variant, condition increasingly diagnosed older first offenders which often missed due absence memory impairment. 3. Introducing natural compounds potentially beneficial illness.

Language: Английский

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Molecular and cellular mechanisms of mitochondria transfer in models of central nervous system disease

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 14, 2024

In the central nervous system (CNS), neuronal function and dysfunction are critically dependent on mitochondrial integrity activity. damaged or diseased brains, reduces adenosine triphosphate (ATP) levels impairs ATP-dependent neural firing neurotransmitter dynamics. Restoring capacity to generate ATP may be fundamental in restoring function. Recent studies animals humans have demonstrated that endogenous mitochondria released into extracellular environment transported exchanged between cells CNS. Under pathological conditions CNS, intercellular transfer contributes new classes of signaling multifunctional cellular activities, thereby triggering deleterious effects promoting beneficial responses. Therefore, take full advantage mitochondria, it useful transplant healthy viable tissues. this review, we describe recent findings mechanisms provide an overview experimental methodologies, including tissue sourcing, isolation, storage, modification, aimed at optimizing transplantation therapy for CNS disorders. Additionally, examine clinical relevance potential strategies therapeutic application transplantation.

Language: Английский

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ER-organelle contacts: A signaling hub for neurological diseases

Pharmacological Research, Journal Year: 2024, Volume and Issue: 203, P. 107149 - 107149

Published: March 20, 2024

Neuronal health is closely linked to the homeostasis of intracellular organelles, and organelle dysfunction affects pathological progression neurological diseases. In contrast isolated cellular compartments, a growing number studies have found that organelles are largely interdependent structures capable communicating through membrane contact sites (MCSs). MCSs been identified as key pathways mediating inter-organelle communication crosstalk in neurons, their alterations disease pathology. The endoplasmic reticulum (ER) membrane-bound forming an extensive network pools tubules with important physiological functions within neurons. There multiple between ER other plasma (PM), which regulate variety processes. this review, we focus on ER-organelle role We compared biological effects different tethering proteins respective counterparts. also discuss how altered contacts may affect pathogenesis. Therefore, understanding molecular mechanisms neuronal will lay foundation for development new therapies targeting contacts.

Language: Английский

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

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

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, contributing to repair processes. Whether hNSCs communicate through TNTs and their role in neuroprotection remain 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, though which they functional mitochondria. Co-culturing with neurons revealed heterotypic allowing mitochondrial neurons. 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 mitochondria neurons, 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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Mitochondrial Transfer in the Neurovascular Unit, Not Only for Energy Rescue: A Systematic Review

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Despite substantial evidence highlighting molecular communication within the components of neurovascular units (NVU), interactions at organelle level have been insufficiently explored in recent decades. Mitochondria, for instance, beyond their traditional role as energy supply intracellular metabolism and survival, provide a novel perspective on intercellular connections through mitochondrial transfer. These transferred mitochondria not only carry bioactive molecules but also signal to mitigate risks both healthy pathological conditions. In this review, we summarized transfer events, relevant routes, underlying mechanisms originating from diverse cell populations NVU. We particularly focus therapeutic potential mechanism treating central nervous system disorders, notably neurodegenerative diseases marked by dysfunction then highlight promising prospects exogenous supplementation treatment target.

Language: Английский

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