Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease

Zhang, Qi; Chen, Shuhua; Yu, Shu; Qin, Jing; Zhang, Jingjing; Cheng, Qian; Ke, Kaifu; Ding, Fei

doi:10.1016/j.neuropharm.2016.04.025

Cited by 37 publications

(30 citation statements)

References 32 publications

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“…PD is the second most common neurodegenerative disease and is characterized by a loss of dopaminergic neurons . Some environmental risk factors, such as ROT and MPP + , are used as neurotoxins for evaluating potential neuroprotective strategies against apoptotic diseases like PD . For in vitro PD studies, the SH‐SY5Y human neuroblastoma cell line is frequently used as a cell model, because it exhibits many characteristics of dopaminergic neurons .…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Some environmental risk factors, such as ROT and MPP + , are used as neurotoxins for evaluating potential neuroprotective strategies against apoptotic diseases like PD. [26][27][28][29][30] For in vitro PD studies, the SH-SY5Y human neuroblastoma cell line is frequently used as a cell model, because it exhibits many characteristics of dopaminergic neurons. 31,32 In the present study, we demonstrated that both RBM3 and mild hypothermia protect SH-SY5Y cells from ROT-induced neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

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Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Yang

Zhuang

et al. 2019

J Cellular Molecular Medi

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Mild hypothermia and its key product, cold‐inducible protein RBM3, possess robust neuroprotective effects against various neurotoxins. However, we previously showed that mild hypothermia fails to attenuate the neurotoxicity from MPP+, one of typical neurotoxins related to the increasing risk of Parkinson disease (PD). To better understand the role of mild hypothermia and RBM3 in PD progression, another known PD‐related neurotoxin, rotenone (ROT) was utilized in this study. Using immunoblotting, cell viability assays and TUNEL staining, we revealed that mild hypothermia (32°C) significantly reduced the apoptosis induced by ROT in human neuroblastoma SH‐SY5Y cells, when compared to normothermia (37°C). Meanwhile, the overexpression of RBM3 in SH‐SY5Y cells mimicked the neuroprotective effects of mild hypothermia on ROT‐induced cytotoxicity. Upon ROT stimulation, MAPK signalling like p38, JNK and ERK, and AMPK and GSK‐3β signalling were activated. When RBM3 was overexpressed, only the activation of p38, JNK and ERK signalling was inhibited, leaving AMPK and GSK‐3β signalling unaffected. Similarly, mild hypothermia also inhibited the activation of MAPKs induced by ROT. Lastly, it was demonstrated that the MAPK (especially p38 and ERK) inhibition by their individual inhibitors significantly decreased the neurotoxicity of ROT in SH‐SY5Y cells. In conclusion, these data demonstrate that RBM3 mediates mild hypothermia‐related neuroprotection against ROT by inhibiting the MAPK signalling of p38, JNK and ERK.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Yang

Zhuang

et al. 2019

J Cellular Molecular Medi

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“…PQQ can protect human neuroblastoma SH-SY5Y cells against Aβ-induced neurotoxicity [38] and prevent α-synuclein amyloid fibril formation. PQQ can also increase mitochondrial biogenesis and function, potentially by activation of PGC-1α, ras, DJ-1, Nrf2 and ERK signaling, increasing mitochondrial gene expression and reducing mitochondrial ROS levels [21, 22, 39, 40]. However, it is unlikely that PQQ acts by increasing PGC-1α levels alone, since overexpression of PGC-1α exacerbates amyloid and tau deposition in AD mice [41].…”

Section: Discussionmentioning

confidence: 99%

Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer’s disease

Sawmiller

Mori

et al. 2017

Heliyon

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Alzheimer’s disease (AD), a progressive neurodegenerative disorder, is linked to oxidative stress, altered amyloid precursor protein (APP) proteolysis, tau hyperphosphorylation and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles (NFT). A growing body of evidence suggests that mitochondrial dysfunction can be a key promoter of all of these pathologies and predicts that restoration of mitochondrial function might be a potential therapeutic strategy for AD. Therefore, in the present study, we tested the beneficial effect of a nutraceutical formulation Nutrastem II (Nutra II), containing NT020 (a mitochondrial restorative and antioxidant proprietary formulation) and pyrroloquinolinequinone (PQQ, a stimulator of mitochondria biogenesis) in 5XFAD transgenic mice. Animals were fed Nutra II for 12 weeks, starting at 3 months of age, after which behavioral and neuropathological endpoints were determined. The data from behavioral test batteries clearly revealed that dietary supplementation of Nutra II effectively ameliorated the motor deficiency and cognitive impairment of 5XFAD mice. In addition, Nutra II also protected mitochondrial function in 5XFAD mice brain, as evidenced by declined ROS levels and membrane hyperpolarization, together with elevated ATP levels and respiratory states. Interestingly, while Nutra II treatment only slightly reduced soluble Aβ42 levels, this formulation significantly impacted tau metabolism, as shown by reduced total and phosphorylated tau levels of 5XFAD mouse brain. Taken together, these preclinical findings confirm that mitochondrial function may be a key treatment target for AD and that Nutra II should be further investigated as a potential candidate for AD therapy.

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“…Human SH-SY5Y neuroblastoma cells express multiple markers characteristic for SN dopaminergic neurons in vivo, and produce high levels of dopamine and show high histaminergic gene expression (Korecka et al, 2013). The rotenone induced SH-SY5Y cell is a widely used cellular model of PD (Chiu et al, 2015, Zhang et al, 2016. Cells were obtained from The Cell Bank of Chinese Academy of Sciences.…”

Section: Cell Culture Experiments and Treatmentmentioning

confidence: 99%

Histamine-4 receptor antagonist JNJ7777120 inhibits pro-inflammatory microglia and prevents the progression of Parkinson-like pathology and behaviour in a rat model

Zhou

Homberg

Fang

et al. 2019

Brain, Behavior, and Immunity

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Activation of microglial cells is presumed to play a key role in the pathogenesis of Parkinson's disease (PD). The activity of microglia is regulated by the histamine-4 receptor (H4R), thus providing a novel target to prevent the progression of PD. However, this putative mechanism has so far not been validated. In our previous post-mortem study, we found that mRNA expression of H4R was upregulated in the basal ganglia of PD patients. In the present study, we found indeed an upregulation of microglia associated inflammation markers from microarray data of the substantia nigra pars compacta (SNpc) of PD patients. We validated the mechanism underlying our human PD results using the rotenone-induced PD rat model, in which the expression of H4R and microglial markers mRNA were significantly increased in the SNpc. Inhibition of H4R in rotenone-induced rats by infusion of the specific H4R antagonist JNJ7777120 into the left lateral ventricle blocked microglial activation, reduced apomorphine-induced rotational behaviour, and prevented dopaminergic neuron degeneration and associated decreases in striatal dopamine levels. These changes were accompanied by a reduction of Lewy body-like neuropathology. Our results provide first proof of the efficacy of an H4R antagonist in a commonly used 3 PD rat model, and provides a lead for a promising therapeutic strategy aimed at modifying H4R activation to clinically tackle microglial activation and thereby the progression of PD.

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Neuroprotective effects of pyrroloquinoline quinone against rotenone injury in primary cultured midbrain neurons and in a rat model of Parkinson's disease

Cited by 37 publications

References 32 publications

Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Cold‐inducible protein RBM3 mediates hypothermic neuroprotection against neurotoxin rotenone via inhibition on MAPK signalling

Beneficial effects of a pyrroloquinolinequinone-containing dietary formulation on motor deficiency, cognitive decline and mitochondrial dysfunction in a mouse model of Alzheimer’s disease

Histamine-4 receptor antagonist JNJ7777120 inhibits pro-inflammatory microglia and prevents the progression of Parkinson-like pathology and behaviour in a rat model

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