Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway

Fan, Yue; Li, Yuanlong; Huang, Silin; Xu, Huali; Li, Hui; Liu, Beixing

doi:10.1016/j.neulet.2020.135262

Cited by 46 publications

(37 citation statements)

References 34 publications

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“…In another study, 100 mg/kg of resveratrol (i.p.) exosomes improved motor function by inhibiting apoptosis and activating autophagy through the PI3K signaling pathway [211]. Resveratrol also blocks the Notch signaling pathway to limit SCI [212].…”

Section: Caffeic Acid Phenethylmentioning

confidence: 99%

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Fakhri

Abbaszadeh

Moradi

et al. 2022

Oxidative Medicine and Cellular Longevity

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Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.

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Section: Caffeic Acid Phenethylmentioning

confidence: 99%

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Fakhri

Abbaszadeh

Moradi

et al. 2022

Oxidative Medicine and Cellular Longevity

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show abstract

“…When the PI3K/AKT pathway was activated in the Exo + Res group, the survival rate and autophagy level of nerve cells in the SCI area were increased and the apoptosis level was decreased. It showed a more effective SCI alleviating effect than free resveratrol (Fan et al, 2020). The above evidence shows that the combination of exosomes and TCMs has the potential to treat SCI and has broad prospects in managing SCI.…”

Section: Exosomes As Drug Delivery Vehicles For Traditional Chinese Medicines (Tcms)mentioning

confidence: 86%

Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

Feng

Zhang

Zhu

et al. 2021

Front. Cell Dev. Biol.

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Acute spinal cord injury (SCI) is a serious traumatic event to the spinal cord with considerable morbidity and mortality. This injury leads to short- and long-term variations in the spinal cord, and can have a serious effect on the patient’s sensory, motor, or autonomic functions. Due to the complicated pathological process of SCI, there is currently no successful clinical treatment strategy. Exosomes, extracellular vesicles (EVs) with a double-layer membrane structure of 30–150 nm diameter, have recently been considered as critical mediators for communication between cells and tissues by transferring proteins, lipids, and nucleic acids. Further studies verified that exosomes participate in the pathophysiological process of several diseases, including cancer, neurodegenerative diseases, and cardiovascular diseases, and could have a significant impact in their treatment. As natural carriers of biologically active cargos, exosomes have emerged as pathological mediators of SCI. In this review article, we critically discuss the functions of exosomes as intracellular mediators and potential treatments in SCI and provide an outlook on future research.

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“…Additionally, ATP-mediated Akt/ mTOR/p70S6K pathway activation can promote the improvement of locomotor function after SCI in rats (32); furthermore, MSC derived EVs can increase the ATP levels and cell viability of damaged cells, reduce oxidative stress, and activate the PI3K/Akt pathway to alleviate the severity of cell injury (33). Moreover, resveratrol-primed exosomes can strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K/Akt/mTOR signaling pathway (34). However, the appropriate normalization strategy to compare quantitatively the functions of different EVs with drug therapy remains to be explored in future work because of the complexity of EV cargo content.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from skin precursor-derived Schwann cells promote axonal outgrowth and regeneration of motoneurons via Akt/mTOR/p70S6K pathway

Wu¹,

Wang²,

Ma³

et al. 2020

Ann Transl Med

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Background: Skin precursor-derived Schwann cells (SKP-SCs) have been shown to benefit the recovery of spinal cord injury (SCI) and peripheral nerve injury (PNI) with motor dysfunction. However, the effect of extracellular vesicles (EVs) from SKP-SCs responsible for neuroregeneration remains unknown.Methods: Based on the obtainment and identification of rat SKP-SCs and their derived EVs, the primary rat injury model of motoneurons resulting from axotomy in vitro or nerve crush in vivo, as well as the secondary rat ischemic hypoxic injury model of motoneuron exposure to oxygen-glucose-deprivation (OGD) in vitro, were treated with EVs from skin precursor-derived Schwann cells (SKP-SC-EVs), respectively.Then, the axonal outgrowth and regrowth was observed and compared, and cell viability as well as the protein kinase B/mammalian target of rapamycin/p70 S6 kinase (Akt/mTOR/p70S6K) signaling pathway was detected, moreover, rapamycin (an mTOR inhibitor) was used to further reveal the underlying molecular mechanism.Results: The internalization of SKP-SC-EVs by neuronal cells was identified in vitro and in vivo. Besides the pro-axonal outgrowth effect of SKP-SC-EVs, prospectively, the treatment of OGD-injured motoneurons with SKP-SC-EVs potentiated the restoration of neuronal viability and axonal regrowth. Furthermore, the axotomizing injury could be improved with SKP-SC-EVs treatment in vitro and in vivo. Finally, it was shown that the application of SKP-SC-EVs could activate the Akt/mTOR/p70S6K signaling pathway that can be abolished by rapamycin.Conclusions: In summary, the addition of SKP-SC-EVs could regulate the cell growth and death signaling pathway mediated by Akt/mTOR/p70S6K, owing to the transmission of cargos in EVs to damaged motoneurons, which leads to axonal regrowth and neuronal resurrection. Thus, SKP-SC-EVs treatment could be a novel promising strategy for improving the axonal outgrowth and regeneration of motoneurons.

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Resveratrol-primed exosomes strongly promote the recovery of motor function in SCI rats by activating autophagy and inhibiting apoptosis via the PI3K signaling pathway

Cited by 46 publications

References 34 publications

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

Emerging Exosomes and Exosomal MiRNAs in Spinal Cord Injury

Extracellular vesicles from skin precursor-derived Schwann cells promote axonal outgrowth and regeneration of motoneurons via Akt/mTOR/p70S6K pathway

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