M2 microglia-derived exosomes reduce neuronal ferroptosis via FUNDC1-mediated mitophagy by activating AMPK/ULK1 signaling DOI Creative Commons
Jian Li, Qing Chen,

Hao Gu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: May 23, 2025

Language: Английский

Innovative Insights into Traumatic Brain Injuries: Biomarkers and New Pharmacological Targets DOI Open Access
Serena Silvestro, Ivana Raffaele, Angelo Quartarone

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2372 - 2372

Published: Feb. 17, 2024

A traumatic brain injury (TBI) is a major health issue affecting many people across the world, causing significant morbidity and mortality. TBIs often have long-lasting effects, disrupting daily life functionality. They cause two types of damage to brain: primary secondary. Secondary particularly critical as it involves complex processes unfolding after initial injury. These can lead cell death in brain. Understanding how these crucial for finding new treatments. This review examines wide range literature from 2021 2023, focusing on biomarkers molecular mechanisms pinpoint therapeutic advancements. Baseline levels biomarkers, including neurofilament light chain (NF-L), ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1), Tau, glial fibrillary acidic protein (GFAP) TBI, demonstrated prognostic value cognitive outcomes, laying groundwork personalized treatment strategies. In terms pharmacological progress, most promising approaches currently target neuroinflammation, oxidative stress, apoptotic mechanisms. Agents that modulate pathways offer potential reduce TBI's impact aid neurological rehabilitation. Future research poised refine approaches, potentially revolutionizing TBI treatment.

Language: Английский

Citations

23

Human umbilical cord mesenchymal stem cell‐derived exosome suppresses programmed cell death in traumatic brain injury via PINK1/Parkin‐mediated mitophagy DOI Creative Commons
Li Zhang, Yixing Lin,

Wanshan Bai

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(8), P. 2236 - 2258

Published: March 8, 2023

Abstract Aims Recently, human umbilical cord mesenchymal stem cell (HucMSC)‐derived exosome is a new focus of research in neurological diseases. The present study was aimed to investigate the protective effects HucMSC‐derived both vivo and vitro TBI models. Methods We established mouse neuron models our study. After treatment with exosome, neuroprotection investigated by neurologic severity score (NSS), grip test score, brain water content, cortical lesion volume. Moreover, we determined biochemical morphological changes associated apoptosis, pyroptosis, ferroptosis after TBI. Results revealed that could improve function, decrease cerebral edema, attenuate Furthermore, administration suppressed TBI‐induced death, ferroptosis. In addition, exosome‐activated phosphatase tensin homolog‐induced putative kinase protein 1/Parkinson 2 E3 ubiquitin–protein ligase (PINK1/Parkin) pathway‐mediated mitophagy However, attenuated when inhibited, PINK1 knockdown. Importantly, also decreased activated PINK1/Parkin vitro. Conclusion Our results provided first evidence played key role through mitophagy.

Language: Английский

Citations

39

Mitophagy-related regulated cell death: molecular mechanisms and disease implications DOI Creative Commons

Molin Yang,

Xiang Wei, Xin Yi

et al.

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(7)

Published: July 16, 2024

Abstract During oxidative phosphorylation, mitochondria continuously produce reactive oxygen species (ROS), and untimely ROS clearance can subject to stress, ultimately resulting in mitochondrial damage. Mitophagy is essential for maintaining cellular quality control homeostasis, with activation involving both ubiquitin-dependent ubiquitin-independent pathways. Over the past decade, numerous studies have indicated that different forms of regulated cell death (RCD) are connected mitophagy. These diverse RCD been shown be by mitophagy implicated pathogenesis a variety diseases, such as tumors, degenerative ischemia‒reperfusion injury (IRI). Importantly, targeting regulate has excellent therapeutic potential preclinical trials, expected an effective strategy treatment related diseases. Here, we present summary role RCD, focus on molecular mechanisms which regulates RCD. We also discuss implications mitophagy-related context various

Language: Английский

Citations

16

Plant-derived exosomes as cell homogeneous nanoplatforms for brain biomacromolecules delivery ameliorate mitochondrial dysfunction against Parkinson’s disease DOI
Yang Xu, Ge Yan, Jingyu Zhao

et al.

Nano Today, Journal Year: 2024, Volume and Issue: 58, P. 102438 - 102438

Published: Aug. 13, 2024

Language: Английский

Citations

15

BNIP3-mediated mitophagy attenuates hypoxic–ischemic brain damage in neonatal rats by inhibiting ferroptosis through P62–KEAP1–NRF2 pathway activation to maintain iron and redox homeostasis DOI
Xinxin Wang, Mei Li,

Xiaowen Xu

et al.

Acta Pharmacologica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 23, 2024

Language: Английский

Citations

12

Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy DOI
Bo Xu, Zezhu Zhou, Jiaqi Fang

et al.

Free Radical Biology and Medicine, Journal Year: 2023, Volume and Issue: 208, P. 319 - 333

Published: Aug. 26, 2023

Language: Английский

Citations

18

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells DOI Creative Commons
Wenya Chen, Peipei Wu, Can Jin

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: May 1, 2024

Abstract Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component stem cell potency, overcome drawbacks cell-free therapeutic agent play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture SCs low yield face challenges large-scale production, which hinders clinical translation EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate vivo environment, can not only expand large quantities, but also improve activity EVs, changing content improving effects. In this review, we briefly describe advantages EV-related applications, provide overview 3D finally focus on specific future perspectives different SCs. Graphical

Language: Английский

Citations

7

Exosomal PINK1 from Human Umbilical Cord Mesenchymal Stem Cells Attenuates Neurological Deficits and Inflammatory Responses after Intracerebral Hemorrhage in Mice DOI
Jian‐Liang Li,

Liang Yang,

Lin Zhao

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 4, 2025

This study investigated the therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (huMSCs), focusing on PTEN-induced kinase 1 (PINK1) and its impact exosome efficacy. Postmodification, were administered to a murine model intracranial hemorrhage (ICH). Assessments included brain edema, neurological function, anxiety-like behaviors, inflammatory responses, microglial polarization. We observed that administration control huMSCs significantly reduced water content, indicating reduction in as quantitatively assessed through content analysis. Neurological evaluated using standard scoring system, showed marked improvement animals treated with compared those receiving PINK1-deficient exosomes, highlighting importance PINK1 mediating recovery. Additionally, substantially decreased behaviors Open Field Test, demonstrated by immobility times increased exploratory behavior. Inflammatory response assessments favorable shift levels pro-inflammatory cytokines (MCP-1, IL-1β, TNF-α) anti-inflammatory cytokine IL-10 exosome-treated groups. Furthermore, analysis polarization revealed toward M2 phenotype, evidenced M1 markers (Cd86, Iba1) (Arg1, Cd206) group. Taken together, we found efficacy ICH treatment normal expression. Our findings underscore critical role enhancing huMSC-derived treatment.

Language: Английский

Citations

1

Harnessing the Potential of Exosomes in Therapeutic Interventions for Brain Disorders DOI Open Access
Bai Lu,

Leijie Yu,

Mao‐Sheng Ran

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2491 - 2491

Published: March 11, 2025

Exosomes, which are nano-sized natural vesicles secreted by cells, crucial for intercellular communication and interactions, playing a significant role in various physiological pathological processes. Their characteristics, such as low toxicity immunogenicity, high biocompatibility, remarkable drug delivery capabilities—particularly their capacity to traverse the blood–brain barrier—make exosomes highly promising vehicles administration treatment of brain disorders. This review provides comprehensive overview exosome biogenesis isolation techniques, strategies loading functionalization exosomes, exosome-mediated barrier penetration mechanisms, with particular emphasis on recent advances exosome-based Finally, we address opportunities challenges associated utilizing system brain, summarizing barriers clinical translation proposing future research directions.

Language: Английский

Citations

1

Human neural stem cell-derived exosomes activate PINK1/Parkin pathway to protect against oxidative stress-induced neuronal injury in ischemic stroke DOI Creative Commons
Mengke Zhao, Jiayi Wang,

Shuaiyu Zhu

et al.

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: April 5, 2025

Mitochondria play a critical role in oxidative stress (OS)-induced neuronal injury during ischemic stroke (IS), making them promising therapeutic targets. Mounting evidence underscores the extraordinary promise of exosomes derived from human neural stem cells (hNSCs) management central nervous system (CNS) diseases. Nonetheless, precise mechanisms by which these target mitochondria to ameliorate effects IS remain only partially elucidated. This study investigates protective hNSC (hNSC-Exos) on damage. Using rat model middle cerebral artery occlusion (MCAO) vivo and OS-induced HT22 vitro. Firstly, our research group independently isolated subsequently prepared hNSC-Exos. In vivo, MCAO rats were restored blood flow perfusion simulate ischemia-reperfusion injury, hNSC-Exos injected through stereotaxic injection into brain. Subsequently, evaluated, including histological studies, behavioral assessments. H2O2 was used OS environment MCAO, then its evaluated co-culturing with hNSC-Exos, immunofluorescence staining, western blotting (WB), quantitative real time PCR (qRT-PCR). process exploring specific mechanisms, we utilized RNA sequencing (RNA-seq) detect potential induction mitophagy cells. Afterwards, employed series mitochondrial function assessments autophagy related detection techniques, measuring membrane potential, reactive oxygen species (ROS) levels, transmission electron microscopy (TEM) imaging, monodansylcadaverine (MDC) mCherry-GFP-LC3B staining. addition, further investigated regulatory pathway using inhibitor mdivi-1 knocking out PTEN induced kinase 1 (PINK1) Administration significantly ameliorated brain tissue damage enhanced outcomes rats. treatment led reduction apoptosis facilitated normalization impaired neurogenesis neuroplasticity. Notably, application vitro resulted an upregulation cells, thereby remedying dysfunction. We demonstrate that activate via PINK1/Parkin pathway, improving reducing apoptosis. These findings suggest alleviate regulating pathway. reveals novel cell-derived therapy promoting neuroprotection their as approach for OS-associated CNS diseases, IS.

Language: Английский

Citations

1