Peroxiredoxin 5 prevents amyloid-beta oligomer-induced neuronal cell death by inhibiting ERK–Drp1-mediated mitochondrial fragmentation

Kim, Bokyung; Park, Junghyung; Chang, Kyu‐Tae; Lee, Dong Seok

doi:10.1016/j.freeradbiomed.2015.11.015

Cited by 66 publications

(75 citation statements)

References 59 publications

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“…Excessive mitochondrial fission leads to fragmentation of mitochondria, resulting in mitochondrial dysfunction and ultimately cell death. 58 Parkin results in the accumulation of dysfunctional mitochondria that release ROS, thereby increasing the oxidative stress that is involved in the pathogenesis of several diseases. [61][62][63] We found that PINK1 and Parkin protein levels and mitochondrial Parkin translocation were increased in human NP cells upon compression, which was accompanied by increased colocalization of LC3 and Tom20, indicating mitophagy initiation.…”

Section: Discussionmentioning

confidence: 99%

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

et al. 2020

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Objective Mitochondrial dysfunction, oxidative stress and nucleus pulposus (NP) cell apoptosis are important contributors to the development and pathogenesis of intervertebral disc degeneration (IDD). Here, we comprehensively evaluated the effects of mitochondrial dynamics, mitophagic flux and Nrf2 signalling on the mitochondrial quality control, ROS production and NP cell survival in in vitro and ex vivo compression models of IDD and explored the effects of the mitochondria‐targeted anti‐oxidant MitoQ and its mechanism. Material and methods Human NP cells were exposed to mechanical compression to mimic pathological conditions. Results Compression promoted oxidative stress, mitochondrial dysfunction and NP cell apoptosis. Mechanistically, compression disrupted the mitochondrial fission/fusion balance, inducing fatal fission. Concomitantly, PINK1/Parkin‐mediated mitophagy was activated, whereas mitophagic flux was blocked. Nrf2 anti‐oxidant pathway was insufficiently activated. These caused the damaged mitochondria accumulation and persistent oxidative damage. Moreover, MitoQ restored the mitochondrial dynamics balance, alleviated the impairment of mitophagosome‐lysosome fusion and lysosomal function and enhanced the Nrf2 activity. Consequently, damaged mitochondria were eliminated, redox balance was improved, and cell survival increased. Additionally, MitoQ alleviated IDD in an ex vivo rat compression model. Conclusions These findings suggest that comodulation of mitochondrial dynamics, mitophagic flux and Nrf2 signalling alleviates sustained mitochondrial dysfunction and oxidative stress and represents a promising therapeutic strategy for IDD; furthermore, our results provide evidence that MitoQ might serve as an effective therapeutic agent for this disorder.

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Section: Discussionmentioning

confidence: 99%

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

et al. 2020

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“…Function related to mitochondria NDDS caused due to mitochondrial dysfunction References Peroxiredoxin 5 Prevents Aβ oligomer-induced neuronal cell death by inhibiting ERK-Drp1-mediated mitochondrial fragmentation AD [113] …”

Section: Biomoleculesmentioning

confidence: 99%

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Jha

Kumar

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Mounting evidence suggests a link between metabolic syndrome (MetS) such as diabetes, obesity, non-alcoholic fatty liver disease in the progression of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases (NDDs). For instance, accumulated Aβ oligomer is enhancing neuronal Ca release and neural NO where increased NO level in the brain through post translational modification is modulating the level of insulin production. It has been further confirmed that irrespective of origin; brain insulin resistance triggers a cascade of the neurodegeneration phenomenon which can be aggravated by free reactive oxygen species burden, ER stress, metabolic dysfunction, neuorinflammation, reduced cell survival and altered lipid metabolism. Moreover, several studies confirmed that MetS and diabetic sharing common mechanisms in the progression of AD and NDDs where mitochondrial dynamics playing a critical role. Any mutation in mitochondrial DNA, exposure of environmental toxin, high-calorie intake, homeostasis imbalance, glucolipotoxicity is causative factors for mitochondrial dysfunction. These cumulative pleiotropic burdens in mitochondria leads to insulin resistance, increased ROS production; enhanced stress-related enzymes that is directly linked MetS and diabetes in neurodegeneration. Since, the linkup mechanism between mitochondrial dysfunction and disease phenomenon of both MetS and NDDs is quite intriguing, therefore, it is pertinent for the researchers to identify and implement the therapeutic interventions for targeting MetS and NDDs. Herein, we elucidated the pertinent role of MetS induced mitochondrial dysfunction in neurons and their consequences in NDDs. Further, therapeutic potential of well-known biomolecules and chaperones to target altered mitochondria has been comprehensively documented. This article is part of a Special Issue entitled: Oxidative Stress and Mitochondrial Quality in Diabetes/Obesity and Critical Illness Spectrum of Diseases - edited by P. Hemachandra Reddy.

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“…More than 36 million people older than 65 years were diagnosed as AD worldwide [1]. Amyloid β (Aβ) plays key roles in AD pathogenesis via regulating neuronal cell death [5, 6]. It was reported that the continuous production, degradation and the aggregation of amyloid beta-protein (Aβ) lead to AD [7].…”

Section: Introductionmentioning

confidence: 99%

Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

Yang

Cui

et al. 2017

PLoS ONE

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BackgroundAlzheimer's disease (AD) is one of the most common neurodegenerative disorders. Recent studies have shown that mitochondrial dysfunction is a causative factor of AD. Drp1 (Dynamin-related protein 1), a regulator of mitochondrial fission, shows neuroprotective effects on Parkinson’s disease. In this study, we investigate the effect and mechanism of Drp1 on Aβ42 transgenic Drosophila.MethodsElav-gal4/UAS>Aβ42 transgenic Drosophila model was constructed using Elav-gal4 promoter. The effects of Drp1 on the lifespan, motor ability and neuronal degeneration of the transgenic Drosophila were explored by over-expressing Drp1 in the Aβ42 transgenic Drosophila. ATP levels in the brain tissues of Aβ42 transgenic Drosophila were detected using high performance liquid chromatography (HPLC).ResultsExogenous expression of Drp1 promoted crawling ability, reduced the levels of ATP in Drosophila brain and suppressed the neuronal degeneration.ConclusionThe protective effect of Drp1 on the Aβ42 transgenic Drosophila was achieved by protecting the mitochondrial function, suggesting that Drp1 may be a potential therapeutic strategies for AD.

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Peroxiredoxin 5 prevents amyloid-beta oligomer-induced neuronal cell death by inhibiting ERK–Drp1-mediated mitochondrial fragmentation

Cited by 66 publications

References 59 publications

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

The mitochondria‐targeted anti‐oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance

Linking mitochondrial dysfunction, metabolic syndrome and stress signaling in Neurodegeneration

Exogenous expression of Drp1 plays neuroprotective roles in the Alzheimer's disease in the Aβ42 transgenic Drosophila model

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