Parkin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration

Zhang, Zengjie; Xu, Tianzhen; Chen, Jiaoxiang; Shao, Zewei; Wang, Ke; Yan, Yingchao; Wu, Congcong; Lin, Jialiang; Wang, Haoli; Gao, Weiyang; Zhang, Xiaolei; Wang, Xiangyang

doi:10.1038/s41419-018-1024-9

Cited by 77 publications

(78 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…salidroside is also beneficial for IVDD in rats through the role of PRKN [17]. Their data indicate the role of PRKN in the eliminating of damaged mitochondria and NP cells survival.…”

Section: The Roles Of Mitophagy In Ivddmentioning

confidence: 86%

Mitophagy in degenerative joint diseases

et al. 2020

View full text Add to dashboard Cite

Mitochondrial dysfunction is involved in aging and multiple degenerative diseases, including intervertebral disc degeneration (IVDD) and osteoarthritis (OA). Thus, the maintenance of mitochondria homeostasis and function is important. Mitophagy, a process that selectively clears damaged or dysfunctional mitochondria through autophagic machinery, functions to maintain mitochondrial quality control and homeostasis. IVDD and OA are similar joint diseases involving the degradation of cartilaginous tissues that are mainly caused by oxidative stress, cell apoptosis and extracellular matrix (ECM) degradation. Over the past decade, accumulating evidence indicates the essential role of mitophagy in the pathogenesis of IVDD and OA. Importantly, strategies by the regulation of mitophagy exert beneficial effects in the pre-clinical experiments. Given the importance and novelty of mitophagy, we provide an overview of mitophagy pathways and discuss the roles of mitophagy in IVDD and OA. We also highlight the potential of targeting mitophagy for the treatment of degenerative joint diseases.

show abstract

“…salidroside is also beneficial for IVDD in rats through the role of PRKN [17]. Their data indicate the role of PRKN in the eliminating of damaged mitochondria and NP cells survival.…”

Section: The Roles Of Mitophagy In Ivddmentioning

confidence: 86%

Mitophagy in degenerative joint diseases

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In MPTP-induced Parkinson's disease models, Sal can enhance the mitochondrial expression of PINK1 and Parkin and confer neuroprotective effects [31]. Another study showed that upregulation of Parkin by Sal promoted the survival of nucleus pulposus cells through activation of mitophagy in vitro [74]. Therefore, we evaluated the occurrence of mitophagy in Sal after SCIRI.…”

Section: Discussionmentioning

confidence: 99%

Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy

Huang

et al. 2020

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Ischemia-reperfusion injury is the second most common injury of the spinal cord and has the risk of neurological dysfunction and paralysis, which can seriously affect patient quality of life. Salidroside (Sal) is an active ingredient extracted from Herba Cistanche with a variety of biological attributes such as antioxidant, antiapoptotic, and neuroprotective activities. Moreover, Sal has shown a protective effect in ischemia-reperfusion injury of the liver, heart, and brain, but its effect in ischemia-reperfusion injury of the spinal cord has not been elucidated. Here, we demonstrated for the first time that Sal pretreatment can significantly improve functional recovery in mice after spinal cord ischemia-reperfusion injury and significantly inhibit the apoptosis of neurons both in vivo and in vitro. Neurons have a high metabolic rate, and consequently, mitochondria, as the main energy-supplying suborganelles, become the main injury site of spinal cord ischemia-reperfusion injury. Mitochondrial pathway-dependent neuronal apoptosis is increasingly confirmed by researchers; therefore, Sal’s effect on mitochondria naturally attracted our attention. By means of a range of experiments both in vivo and in vitro, we found that Sal can reduce reactive oxygen species production through antioxidant stress to reduce mitochondrial permeability and mitochondrial damage, and it can also enhance the PINK1-Parkin signaling pathway and promote mitophagy to eliminate damaged mitochondria. In conclusion, our results show that Sal is beneficial to the protection of spinal cord neurons after ischemia-reperfusion injury, mainly by reducing apoptosis associated with the mitochondrial-dependent pathway, among which Sal’s antioxidant and autophagy-promoting properties play an important role.

show abstract

“…PINK1/ Parkin mitophagy pathway has been identified as a classical pathway involved in mitophagy 48 . Zhang et al reported that Parkin was involved in the pathogenesis of IVDD and may be potential therapeutic target for IVDD 49 . PINK1, Parkin and LC3 II are key proteins for mitophagy initiation, and p62 is indispensable for autophagic degradation 50 .…”

Section: Discussionmentioning

confidence: 99%

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

et al. 2019

View full text Add to dashboard Cite

The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.

show abstract

Parkin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration

Cited by 77 publications

References 48 publications

Mitophagy in degenerative joint diseases

Mitophagy in degenerative joint diseases

Salidroside Ameliorates Mitochondria-Dependent Neuronal Apoptosis after Spinal Cord Ischemia-Reperfusion Injury Partially through Inhibiting Oxidative Stress and Promoting Mitophagy

CircERCC2 ameliorated intervertebral disc degeneration by regulating mitophagy and apoptosis through miR-182-5p/SIRT1 axis

Contact Info

Product

Resources

About