Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model

Ortega-Arellano, Hector Flavio; Jiménez-Del-Río, Marlene; Vélez-Pardo, Carlos

doi:10.1590/s1415-47572013000400020

Cited by 19 publications

(11 citation statements)

References 55 publications

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“…Our data show that JNK is activated by phosphorylation following PQ treatment, while pharmacological inhibition of JNK increases survival in WT flies. In accordance with our data, knockdown of the basket gene in the dopaminergic neurons has been shown to improve survival and climbing ability in Drosophila 68 . Prolonged JNK activation has been implicated in exacerbating disease phenotypes in both AD and PD models 69,70 .…”

Section: Discussionsupporting

confidence: 91%

Innate immune responses to paraquat exposure in a Drosophila model of Parkinson’s disease

Maitra

Scaglione

Chtarbanova

et al. 2019

Sci Rep

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Parkinson’s disease (PD) is a progressive, neurodegenerative movement disorder characterized by the loss of dopaminergic (DA) neurons. Limited understanding of the early molecular pathways associated with the demise of DA neurons, including those of inflammatory exacerbation of neurodegeneration, is a major impediment to therapeutic development. Recent studies have implicated gene-environment interactions in PD susceptibility. We used transcriptomic profiling in a Drosophila PD model in response to paraquat (PQ)-induced oxidative stress to identify pre-symptomatic signatures of impending neuron dysfunction. Our RNAseq data analysis revealed extensive regulation of innate immune response genes following PQ ingestion. We found that PQ exposure leads to the activation of the NF-κB transcription factor, Relish, and the stress signaling factor JNK, encoded by the gene basket in Drosophila . Relish knockdown in the dopaminergic neurons confers PQ resistance and rescues mobility defects and DA neuron loss. Furthermore, PQ-induced toxicity is mediated through the immune deficiency signaling pathway. Surprisingly, the expression of Relish-dependent anti-microbial peptide (AMPs) genes is suppressed upon PQ exposure causing increased sensitivity to Gram-negative bacterial infection. This work provides a novel link between PQ exposure and innate immune system modulation underlying environmental toxin-induced neurodegeneration, thereby underscoring the role of the innate immune system in PD pathogenesis.

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Section: Discussionsupporting

confidence: 91%

Innate immune responses to paraquat exposure in a Drosophila model of Parkinson’s disease

Maitra

Scaglione

Chtarbanova

et al. 2019

Sci Rep

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“…The previous outcome may be attributed to the polyphenolic and other phytochemical constituents that were recorded in the GC-MS analysis of PSE and PJ. Our results were in agreement with Ortega-Arellano et al [ 46 ] who recorded a protective effect of polyphenols against PQ in Drosophila.…”

Section: Discussionsupporting

confidence: 94%

“…Apoptosis or programmed cell death was potentiated following PQ administration into Drosophila melanogaster via the oxidative stress-induced pathway [ 46 ]. The molecular cascades for apoptosis were inferred to ROS production and chromatin condensation/DNA fragmentation [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of pomegranate (Punica granatum L.) juice and seed extract in paraquat-induced mouse model of Parkinson’s disease

Fathy

El-Dash

Said

2021

BMC Complement Med Ther

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Background Paraquat, (PQ), an herbicide that can induce Parkinsonian-like symptoms in rodents and humans. The consumption of phytochemical-rich plants can reduce the risk of chronic illnesses such as inflammation and neurodegenerative diseases. The present study aimed to investigate the protective effects of pomegranate seed extract (PSE) and juice (PJ) against PQ-induced neurotoxicity in mice. Methods Mice were assigned into 4 groups; three groups received PQ (10 mg/kg, i.p.) twice a week for 3 weeks. Two of the PQ-induced groups pretreated with either PSE or PJ. Detection of phytochemicals, total phenolics, and total flavonoids in PSE and PJ was performed. Tyrosine hydroxylase (TH) level was measured in the substantia nigra (SN) by Western blotting technique. Striatal dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were detected using high-performance liquid chromatography (HPLC). The levels of adenosine triphosphate (ATP), malondialdehyde (MDA), and the activity of the antioxidant enzymes were estimated in the striatum by colorimetric analysis. Striatal pro-inflammatory and anti-inflammatory markers using enzyme-linked immunosorbent assay (ELISA) as well as DNA fragmentation degree by qualitative DNA fragmentation assay, were evaluated. Real-time polymerase chain reaction (qPCR) assay was performed for the detection of nuclear factor kappa B (NF-кB) gene expression. Moreover, Western blotting analysis was used for the estimation of the cluster of differentiation 11b (CD11b), transforming growth factor β (TGF-β), and glial cell-derived neurotrophic factor (GDNF) levels in the striatum. Results Pretreatment with PSE or PJ increased the levels of TH in the SN as well as DA and its metabolite in the striatum that were reduced by PQ injection. PSE and PJ preadministration improved the PQ-induced oxidative stress via a significant reduction of the MDA level and the augmentation of antioxidant enzyme activities. PSE and PJ also significantly downregulated the striatal NF-кB gene expression, reduced the PQ-enhanced apoptosis, decreased the levels of; pro-inflammatory cytokines, CD11b, and TGF-β coupled with a significant increase of; interleukin-10 (IL-10), GDNF, and ATP levels as compared with PQ-treated mice. Conclusions The current study indicated that PSE and PJ consumption may exhibit protective effects against PQ-induced neurotoxicity in mice.

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“…Furthermore, polyphenols are identified to be neuroprotective for multiple human neurodegenerative diseases including PD, Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS) [50]. It was reported that polyphenols, including GA, propyl gallate (PG), epicatechin (EC), EGC, and EGCG, can protect DA neurons and restore the impaired movement activity induced by iron and/or paraquat (PQ) challenges in Drosophila PD model [51,52]. Furthermore, green and black tea polyphenol extracts, as well as EGCG, were identified to be able to protect against MPTP or 6-OHDA challenges induced DA neurons degeneration in mice, rats and monkey PD models [53,54].…”

Section: Discussionmentioning

confidence: 99%

The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)

Zhou

Xie

Saw

et al. 2019

Cells

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: Accumulative evidence indicated that the pathologically accumulated metal ions (iron species and Mn3+) and abnormally up-regulated monoamine oxidase B (MAOB) activity induced oxidation of endogenous dopamine (DA) can lead to mitochondria impairment, lysosome dysfunction, proteasome inhibition, and selective DA neuron vulnerability, which is implicated in the pathogenesis of Parkinson’s disease (PD). The DA oxidation can generate deleterious reactive oxygen species (ROS) and highly reactive DA quinones (DAQ) to induce DA-related toxicity, which can be alleviated by DA oxidation suppressors, ROS scavengers, DAQ quenchers, and MAOB inhibitors. On the other hand, the nuclear factor erythroid 2-related factor 2 (Nrf2)-Keap1 and Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) anti-oxidative and proliferative signaling pathways play roles in anti-oxidative cell defense and mitochondria biogenesis, which is implicated in DA neuron protections. Therefore, agents with capabilities to suppress DA-related toxicity including inhibition of DA oxidation, scavenge of ROS, detoxification of DAQ, inhibition of MAOB, and modulations of anti-oxidative signaling pathways can be protective to DA neurons. Accumulative evidence shows that tea or coffee consumptions and smoking are related to deceased PD prevalence with unknown mechanisms. In this study, we investigate the protective capabilities of tea polyphenols and other PD relevant agents to inhibit DA-related toxicity and protect against environmental or genetic factors induced DA neuron degeneration in vitro and in vivo. We find that tea polyphenols can significantly suppress DA-related toxicity to protect DA neurons. The tea polyphenols can protect DA neurons via inhibition of DA oxidation, conjugation with DAQ, scavenge of ROS, inhibition of MAOB, and modulations of Nrf2-Keap1 and PGC-1α anti-oxidative signaling pathways. The tea polyphenols with more phenolic hydroxyl groups and ring structures have stronger protective functions. The protective capabilities of tea polyphenols is further strengthened by evidence that phenolic hydroxyl groups can directly conjugate with DAQ. However, GSH and other sulfhydyl groups containing agents have weaker capabilities to abrogate DA oxidation, detoxify ROS and DAQ and inhibit MAOB; whereas nicotine (NICO) and caffeine (CAF) can only modulate Nrf2-Keap1 and PGC-1α pathways to protect DA neurons weakly. The tea polyphenols are identified to protect against overexpression of mutant A30P α-synuclein (α-syn) induced DA neuron degeneration and PD-like symptoms in transgenic Drosophila. Based on achievements from current studies, the excellent and versatile protective capabilities of tea polyphenols are highlighted, which will contribute and benefit to future anti-PD therapy.

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Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model

Cited by 19 publications

References 55 publications

Innate immune responses to paraquat exposure in a Drosophila model of Parkinson’s disease

Innate immune responses to paraquat exposure in a Drosophila model of Parkinson’s disease

Neuroprotective effects of pomegranate (Punica granatum L.) juice and seed extract in paraquat-induced mouse model of Parkinson’s disease

The Therapeutic Implications of Tea Polyphenols against Dopamine (DA) Neuron Degeneration in Parkinson’s Disease (PD)

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