Current progress of mitochondrial transplantation that promotes neuronal regeneration

Chang, Chien-Chi; Liang, Min-Zong; Chen, Linyi

doi:10.1186/s40035-019-0158-8

Cited by 85 publications

(58 citation statements)

References 101 publications

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“…There is currently no remedy for SC intoxication, except for supportive care [70]; however, the oxidative stress mechanistic pathway suggests the possibility of efficacious antioxidant pharmacotherapies for attenuating SC-induced ROS production [71]. Considering that mitochondrial dysfunction plays a critical part in SC-induced neurotoxicity, the enhancement of mitochondrial function [72] and mitochondrial transplantation [73] have received attention as strategies that might ameliorate the associated mitochondrial neurodegeneration. Moreover, the development of therapeutic strategies that stabilize neuronal Ca 2+ homeostasis by targeting the calcium channels may also be capable of preventing neurotoxicity induced by these SCs [74].…”

Section: Discussionmentioning

confidence: 99%

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Leong

Philp

Simone

et al. 2020

IJMS

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Increasing reports of neurological and psychiatric complications due to psychostimulant synthetic cathinones (SCs) have recently raised public concern. However, the precise mechanism of SC toxicity is unclear. This paucity of understanding highlights the need to investigate the in-vitro toxicity and mechanistic pathways of three SCs: butylone, pentylone, and 3,4-Methylenedioxypyrovalerone (MDPV). Human neuronal cells of SH-SY5Y were cultured in supplemented DMEM/F12 media and differentiated to a neuronal phenotype using retinoic acid (10 μM) and 12-O-tetradecanoylphorbol-13-acetate (81 nM). Trypan blue and lactate dehydrogenase assays were utilized to assess the neurotoxicity potential and potency of these three SCs. To investigate the underlying neurotoxicity mechanisms, measurements included markers of oxidative stress, mitochondrial bioenergetics, and intracellular calcium (Ca2+), and cell death pathways were evaluated at two doses (EC15 and EC40), for each drug tested. Following 24 h of treatment, all three SCs exhibited a dose-dependent neurotoxicity, characterized by a significant (p < 0.0001 vs. control) production of reactive oxygen species, decreased mitochondrial bioenergetics, and increased intracellular Ca2+ concentrations. The activation of caspases 3 and 7 implicated the orchestration of mitochondrial-mediated neurotoxicity mechanisms for these SCs. Identifying novel therapeutic agents to enhance an altered mitochondrial function may help in the treatment of acute-neurological complications arising from the illicit use of these SCs.

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Section: Discussionmentioning

confidence: 99%

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Leong

Philp

Simone

et al. 2020

IJMS

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“…Further, the time of mitochondria transfer could be reduced. The possibility to use synaptosomes as delivery system for mitochondria agrees with the suggested possibility to encapsulate isolated mitochondria in biomaterials for improving their delivery to the brain and subsequent uptake by cells [37]. In addition, to load antioxidant molecules, such as curcumin, within synaptosomes could be an additional strategy to protect mitochondria by stress occurring during their transfer and/or into the beneficiary cells.…”

Section: Discussionmentioning

confidence: 55%

“…Although mitochondrial supplementation has been mainly utilized for cardiac injuries, this approach has been also applied for treatment of neurodegenerative disease and other injuries of the nervous system. [19,29,37]. In brain, use of synaptosomes could improve the mitochondrial delivery by protecting the organelle during the transfer, facilitating their specific cellular uptake and reducing stress in the recipient cells.…”

Section: Discussionmentioning

confidence: 99%

Synaptosomes: New Vesicles for Neuronal Mitochondrial Transplantation

Picone

Porcelli

Bavisotto

et al. 2020

Preprint

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Background: Mitochondrial dysfunction is a critical factor in the onset and progression of neurodegenerative diseases. Recently, mitochondrial transplantation has been advised as an innovative and attractive strategy to transfer and replace damaged mitochondria. Here we propose, for the first time, to use rat brain extracted synaptosomes, subcellular fraction of isolated synaptic terminal that contain mitochondria, as mitochondrial delivery systems. Results: Synaptosomes preparation was validated by the presence of Synaptophysin and PSD95. Syn aptosomes were characterized in terms of dimension, zeta potential, polydispersity index and number of particles/mL. Nile Red or CTX-FITCH labeled synaptosomes were internalized in LAN5 recipient cells by a mechanism involving specific protein-protein interaction, as demonstrated by loss of fusion ability after trypsin treatment and using different cell lines. The loading and release ability of the synaptosomes was proved by the presence of curcumin both into synaptosomes and LAN5 cells. The vitality of mitochondria transferred by Synaptosomes was demonstrated by the presence of Opa1, Fis1 and TOM40 mitochondrial proteins and JC-1 measurements. Further, synaptosomes deliver vital mitochondria into the cytoplasm of neuronal cells as demonstrated by microscopic images, increase of TOM 40, cytochrome c, Hexokinase II mitochondrial proteins, and presence of rat mitochondrial DNA. Finally, by using synaptosomes as vehicle, healthy mitochondria restored mitochondrial function in cells containing rotenone or CCCp damaged mitochondria. Conclusions: Taken together these results suggest that synaptosomes can be a natural vehicle for the delivery of molecules and organelles to neuronal cells. Further, replacement of affected mitochondria with healthy ones could be a potential therapy for the treatment of neuronal mitochondrial dysfunction-related diseases.

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“…In recent years, mitochondrial transplantation has shed a new light of therapeutic intervention that benefits neuronal survival and regeneration for neurodegenerative diseases, stroke, and CNS injury. Exogenous healthy mitochondria transplant to defective neurons and promote neuronal viability, activity and neurite re-growth [37][38][39]. In this study, mtDNA-depleted motor neuron NSC-34…”

Section: Discussionmentioning

confidence: 86%

Mitochondria Dynamically Transplant into Cells in Vitro and in Mice and Rescue Aerobic Respiration of Mitochondrial DNA-Depleted Motor Neuron NSC-34

Jiang¹,

Baucom²,

Elliott³

2020

JBiSE

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It has been reported that transplantation of pheochromocytoma P12 and hepatoma cells' mitochondria improve the locomotive activity and prevent disease progress in experimental Parkinson's disease rats. To prepare for mitochondrial transplantation study in human neurodegenerative diseases, we select human fibroblasts as mitochondrial donor because that fibroblasts share many characteristics with mesenchymal stromal cells (MSCs). We isolate human primary fibroblasts and develop a mitochondrial DNA (mtDNA)-depleted mouse motor neuron NSC-34 cells (NSC-34 ρ˚ cells). Fibroblast and NSC-34 cell's mitochondria are co-cultured with NSC-34 ρ˚ cells. Mitochondrial transplantation is observed by fluorescent microscopy. Gene expression is determined by polymerase chain reaction (PCR) and real time PCR (qPCR). Also, mitochondria are injected to mice bearing mammary adenocarcinoma 4T1 cells. We find results as following: 1) There are abundant mitochondria in fibroblasts (337 ± 80 mitochondria per fibroblast). 42.4% of viable mitochondria are obtained by using differential centrifugation. The isolated mitochondria actively transplant into NSC-34 ρ˚ cells after co-culture. 2) Fibroblasts transfer mitochondria to human mammary adenocarcinoma MCF-7 cells. 3) There is no expression of HLA-I antigen in fibroblast's mitochondria indicating they can be used for allogeneic mitochondrial transplantation without HLA antigen match. 4) PCR and qPCR show that NSC-34 ρ˚ cells lose mitochondrially encoded cytochrome c oxidase I (MT-CO1) and mitochondrially encoded NADH dehydrogenase 1 (MT-ND1) and upregulate expression of glycolysis-associated genes hexokinase (HK2), glucose transporter 1 (SLC2A1) and lactate dehydrogenase A (LDHA). 5) Transplantation of NSC-34 mitochondria restores MT-CO1 and MT-ND1 and downregulates gene expression of HK2, SLC2A1 and LDHA. 6) Normal mammary epithelial mitochondria

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Current progress of mitochondrial transplantation that promotes neuronal regeneration

Cited by 85 publications

References 101 publications

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Synthetic Cathinones Induce Cell Death in Dopaminergic SH-SY5Y Cells via Stimulating Mitochondrial Dysfunction

Synaptosomes: New Vesicles for Neuronal Mitochondrial Transplantation

Mitochondria Dynamically Transplant into Cells in Vitro and in Mice and Rescue Aerobic Respiration of Mitochondrial DNA-Depleted Motor Neuron NSC-34

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