Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury

Li, Qiang; Gao, Shane; Kang, Zhanrong; Zhang, Meiyan; Zhao, Xin; Yu, Zhengquan; Huang, Jianming; Yang, Guo‐Yuan; Sun, Wanju; Wang, Jian

doi:10.3389/fnins.2018.00865

Cited by 91 publications

(57 citation statements)

References 36 publications

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“…Mitophagy can negatively regulate IL-1β secretion, and thus inflammatory activation, to protect against TBI-triggered immunopathology [289]. The neuroprotective effects of mitophagy have also been demonstrated in spinal cord injury, which can be induced by inhibition of miRNA-124 or autophagy inducers, such as rapamycin [292][293][294].…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

Selective autophagy as a therapeutic target for neurological diseases

Ocak

Gao

et al. 2020

Cell. Mol. Life Sci.

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The neurological diseases primarily include acute injuries, chronic neurodegeneration, and others (e.g., infectious diseases of the central nervous system). Autophagy is a housekeeping process responsible for the bulk degradation of misfolded protein aggregates and damaged organelles through the lysosomal machinery. Recent studies have suggested that autophagy, particularly selective autophagy, such as mitophagy, pexophagy, ER-phagy, ribophagy, lipophagy, etc., is closely implicated in neurological diseases. These forms of selective autophagy are controlled by a group of important proteins, including PTEN-induced kinase 1 (PINK1), Parkin, p62, optineurin (OPTN), neighbor of BRCA1 gene 1 (NBR1), and nuclear fragile X mental retardation-interacting protein 1 (NUFIP1). This review highlights the characteristics and underlying mechanisms of different types of selective autophagy, and their implications in various forms of neurological diseases.

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Section: Traumatic Brain Injurymentioning

confidence: 99%

Selective autophagy as a therapeutic target for neurological diseases

Ocak

Gao

et al. 2020

Cell. Mol. Life Sci.

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“…In the early stage of spinal cord ischemiareperfusion, enhanced mitophagy can inhibit neuronal apoptosis and alleviate the symptoms of spinal cord injury. 22,[44][45][46] This study found that GIT1 played a regulatory role in mitophagy. GIT1 is vital in the development of mitochondria in the heart, but its role in neurons is unknown.…”

Section: Discussionmentioning

confidence: 58%

The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

Huang

Qian

et al. 2019

FASEB j.

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In spinal cord ischemia‐reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2–interacting protein‐1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia‐reperfusion. However, the overexpression of adeno‐associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin‐1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN‐induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia‐reperfusion injury and, hence, might serve as a new research site for the protection of ischemia‐reperfusion injury.

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“…More generally, rapamycin has demonstrated beneficial effects in the context of acute CNS damage showing increased neuronal survival after spinal cord or brain injury as well as RGC rescue after optic nerve transection and ischaemia/reperfusion 36,56 . Rapamycin is well known to increase autophagy, and also upregulates mitophagy and mitochondrial fission in in vivo CNS damage models [73][74][75][76] . Supporting possible increase of mitophagy after ONC, EM pictures of RGCs after optic nerve transection show increased numbers of mitochondria in autolysosomes 6 days after the insult 36 .…”

Section: Discussionmentioning

confidence: 99%

Age related retinal Ganglion cell susceptibility in context of autophagy deficiency

et al. 2020

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Glaucoma is a common age-related disease leading to progressive retinal ganglion cell (RGC) death, visual field defects and vision loss and is the second leading cause of blindness in the elderly worldwide. Mitochondrial dysfunction and impaired autophagy have been linked to glaucoma and induction of autophagy shows neuroprotective effects in glaucoma animal models. We have shown that autophagy decreases with aging in the retina and that autophagy can be neuroprotective for RGCs, but it is currently unknown how aging and autophagy deficiency impact RGCs susceptibility and survival. Using the optic nerve crush model in young and olWelcome@1234d Ambra1 +/gt (autophagy/beclin-1 regulator 1 +/gt) mice we analysed the contribution of autophagy deficiency on retinal ganglion cell survival in an age dependent context. Interestingly, old Ambra1 +/gt mice showed decreased RGC survival after optic nerve crush in comparison to old Ambra1 +/+ , an effect that was not observed in the young animals. Proteomics and mRNA expression data point towards altered oxidative stress response and mitochondrial alterations in old Ambra1 +/gt animals. This effect is intensified after RGC axonal damage, resulting in reduced oxidative stress response showing decreased levels of Nqo1, as well as failure of Nrf2 induction in the old Ambra1 +/gt. Old Ambra1 +/gt also failed to show increase in Bnip3l and Bnip3 expression after optic nerve crush, a response that is found in the Ambra1 +/+ controls. Primary RGCs derived from Ambra1 +/gt mice show decreased neurite projection and increased levels of apoptosis in comparison to Ambra1 +/+ animals. Our results lead to the conclusion that oxidative stress response pathways are altered in old Ambra1 +/gt mice leading to impaired damage responses upon additional external stress factors.

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Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury

Cited by 91 publications

References 36 publications

Selective autophagy as a therapeutic target for neurological diseases

Selective autophagy as a therapeutic target for neurological diseases

The protective effort of GPCR kinase 2–interacting protein‐1 in neurons via promoting Beclin1‐Parkin induced mitophagy at the early stage of spinal cord ischemia‐reperfusion injury

Age related retinal Ganglion cell susceptibility in context of autophagy deficiency

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