scholarly journals Regulation of Actg1 and Gsta2 is possible mechanism by which capsaicin alleviates apoptosis in cell model of 6-OHDA-induced Parkinson's disease

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Jiahui Liu ◽  
Hong Liu ◽  
Zhenxiang Zhao ◽  
Jianfeng Wang ◽  
Dandan Guo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Model ◽  
Cell Damage ◽  
Glutathione S Transferase ◽  
Expression Arrays ◽  
Transcriptional Changes ◽  
Molecular Mechanism Of Action ◽  
Disease Cell

Abstract The present study aimed to identify the gene expression changes conferred by capsaicin in the cell model of 6-OHDA-induced Parkinson's disease, to disclose the molecular mechanism of action of capsaicin. We used capsaicin-treated and paraffin-embedded wax blocks containing substantia nigra tissue from 6-OHDA-induced Parkinson's disease rats to analyze transcriptional changes using Affymetrix GeneChip Whole Transcript Expression Arrays. A total of 108 genes were differentially expressed in response to capsaicin treatment, and seven of these genes were selected for further analysis: Olr724, COX1, Gsta2, Rab5a, Potef, Actg1, and Acadsb, of which Actg1 (actin gamma 1) was down-regulated and Gsta2 (Glutathione S-transferase alpha 2) was up-regulated. We successfully overexpressed Actg1 and Gsta2 in vitro. CCK-8 detection and flow cytometry demonstrated that overexpression of Actg1 and Gsta2 increased apoptosis in the 6-OHDA-induced Parkinson's disease cell model. The imbalance between Actg1 and Gsta2 may be one of the mechanisms of cell damage in Parkinson's disease (PD). Capsaicin can protect the cells and reduce the apoptosis rate by regulating Actg1 and Gsta2.

scholarly journals Impact of Glucocorticoid on a Cellular Model of Parkinson’s Disease: Oxidative Stress and Mitochondrial Function

2021 ◽  
Vol 11 (8) ◽  
pp. 1106
Author(s):  
Silvia Claros ◽  
Antonio Gil ◽  
Mauro Martinelli ◽  
Nadia Valverde ◽  
Estrella Lara ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Function ◽  
Cell Model ◽  
Cell Damage ◽  
Neuronal Cell ◽  
Cellular Markers ◽  
The Impact

Stress seems to contribute to the neuropathology of Parkinson’s disease (PD), possibly by dysregulation of the hypothalamic–pituitary–adrenal axis. Oxidative distress and mitochondrial dysfunction are key factors involved in the pathophysiology of PD and neuronal glucocorticoid-induced toxicity. Animal PD models have been generated to study the effects of hormonal stress, but no in vitro model has yet been developed. Our aim was to examine the impact of corticosterone (CORT) administration on a dopaminergic neuronal cell model of PD induced by the neurotoxin MPP+, as a new combined PD model based on the marker of endocrine response to stress, CORT, and oxidative-mitochondrial damage. We determined the impact of CORT, MPP+ and their co-incubation on reactive oxygen species production (O2−•), oxidative stress cellular markers (advanced-oxidation protein products and total antioxidant status), mitochondrial function (mitochondrial membrane potential and mitochondrial oxygen consumption rate) and neurodegeneration (Fluoro-Jade staining). Accordingly, the administration of MPP+ or CORT individually led to cell damage compared to controls (p < 0.05), as determined by several methods, whereas their co-incubation produced strong cell damage (p < 0.05). The combined model described here could be appropriate for investigating neuropathological hallmarks and for evaluating potential new therapeutic tools for PD patients suffering mild to moderate emotional stress.

scholarly journals A Novel Long-Noncoding RNA LncZFAS1 Prevents MPP+-Induced Neuroinflammation Through MIB1 Activation

2021 ◽  
Author(s):  
Ziman Zhu ◽  
Peiling Huang ◽  
Ruifeng Sun ◽  
Xiaoling Li ◽  
Wenshan Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Noncoding Rna ◽  
Cell Model ◽  
Developed Countries ◽  
Inflammasome Activation ◽  
Transcriptional Regulatory ◽  
Regulatory Functions

AbstractParkinson’s disease remains one of the leading neurodegenerative diseases in developed countries. Despite well-defined symptomology and pathology, the complexity of Parkinson’s disease prevents a full understanding of its etiological mechanism. Mechanistically, α-synuclein misfolding and aggregation appear to be central for disease progression, but mitochondrial dysfunction, dysfunctional protein clearance and ubiquitin/proteasome systems, and neuroinflammation have also been associated with Parkinson’s disease. Particularly, neuroinflammation, which was initially thought to be a side effect of Parkinson’s disease pathogenesis, has now been recognized as driver of Parkinson’s disease exacerbation. Next-generation sequencing has been used to identify a plethora of long noncoding RNAs (lncRNA) with important transcriptional regulatory functions. Moreover, a myriad of lncRNAs are known to be regulators of inflammatory signaling and neurodegenerative diseases, including IL-1β secretion and Parkinson’s disease. Here, LncZFAS1 was identified as a regulator of inflammasome activation, and pyroptosis in human neuroblast SH-SY5Y cells following MPP+ treatment, a common in vitro Parkinson’s disease cell model. Mechanistically, TXNIP ubiquitination through MIB1 E3 ubiquitin ligase regulates NLRP3 inflammasome activation in neuroblasts. In contrast, MPP+ activates the NLPR3 inflammasome through miR590-3p upregulation and direct interference with MIB1-dependent TXNIP ubiquitination. LncZFAS overexpression inhibits this entire pathway through direct interference with miR590-3p, exposing a novel research idea regarding the mechanism of Parkinson’s disease.

scholarly journals Mitochondrial Gene Therapy Augments Mitochondrial Physiology in a Parkinson's Disease Cell Model

2009 ◽  
Vol 20 (8) ◽  
pp. 897-907 ◽  
Author(s):  
Paula M. Keeney ◽  
Caitlin K. Quigley ◽  
Lisa D. Dunham ◽  
Christina M. Papageorge ◽  
Shilpa Iyer ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Gene Therapy ◽  
Parkinson's Disease ◽  
Cell Model ◽  
Mitochondrial Gene ◽  
Disease Cell

scholarly journals Nur77 attenuates inflammatory responses and oxidative stress by inhibiting phosphorylated IκB-α in Parkinson’s disease cell model

Aging ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 8107-8119
Author(s):  
Junqiang Yan ◽  
Jiarui Huang ◽  
Jiannan Wu ◽  
Hua Fan ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Responses ◽  
Cell Model ◽  
Disease Cell ◽  
And Oxidative Stress

scholarly journals LncRNA SOX2-OT Participates in Parkinson’s Disease Through Regulating miRNA-942-5p/NAIF1 Axis

2021 ◽  
Author(s):  
Yabi Guo ◽  
Yanyang Liu ◽  
Hong Wang ◽  
Peijun Liu
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Apoptosis ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Sod Activity ◽  
Software Analysis ◽  
Direct Target

Abstract Parkinson’s disease (PD) is a neurodegenerative disease. Studies have shown that lncRNA SOX2-OT was highly expressed in PD patients, but its specific functions and mechanisms still need further research. This study aimed to explore whether lncRNA SOX2-OT could regulate oxidative stress, inflammation and neuronal apoptosis in PD in vitro model and explored the underlying mechanism. An in vitro PD cell model was induced by 1-methyl-4-phenylpyridinium (MPP+). The results of the biological software analysis and luciferase reporter assay indicated that miR-942-5p was a direct target of lncRNA SOX2-OT, and NAIF1 was a direct target of miR-942-5p. Experiments showed that the expression levels of lncRNA SOX2-OT and NAIF1 were increased, and miR-942-5p expression was decreased in SH-SY5Y cells following MPP+ treatment. In addition, MPP+ treatment reduced SH-SY5Y cell viability, induced apoptosis, increased cleaved-Caspase3 protein expression, and increased cleaved-Caspase3/Caspase3 ratio, increased LDH viability, and increased the levels of TNF-α, IL-1β and ROS in SH-SY5Y cells, reduced SOD activity, however, all these effects were inhibited by SOX2-OT-siRNA, and these inhibitions were reversed by miR-942-5p inhibitor. Moreover, the protective role of miR-942-5p mimic in MPP+ induced SH-SY5Y cells was significantly eliminated by NAIF1-plasmid. In summary, this study confirmed that lncRNA SOX2-OT regulated oxidative stress, inflammation and neuronal apoptosis via directly regulating the miR-942-5p/NAIF1 signal axis, and then participated in the occurrence and development of PD. These data provide a new potential targets for PD diagnosis and treatment.

scholarly journals Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson’s disease model

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunni Zhu ◽  
Tina Bilousova ◽  
Samantha Focht ◽  
Michael Jun ◽  
Chris Jean Elias ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Motor Function ◽  
Cell Model ◽  
Extracellular Vesicle ◽  
Alpha Synuclein ◽  
Proteinase K ◽  
In Vivo Studies

Abstract Aim We have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro in a cell model and reduced tau seed propagation. The enzyme nSMase2 is involved in the production of exosomes carrying proteopathic seeds and could contribute to cell-to-cell transmission of pathological protein aggregates implicated in neurodegenerative diseases such as Parkinson’s disease (PD). Here, we performed in vivo studies to determine if DDL-112 can reduce brain EV/exosome production and proteopathic alpha synuclein (αSyn) spread in a PD mouse model. Methods The acute effects of single-dose treatment with DDL-112 on interleukin-1β-induced extracellular vesicle (EV) release in brain tissue of Thy1-αSyn PD model mice and chronic effects of 5 week DDL-112 treatment on behavioral/motor function and proteinase K-resistant αSyn aggregates in the PD model were determined. Results/discussion In the acute study, pre-treatment with DDL-112 reduced EV/exosome biogenesis and in the chronic study, treatment with DDL-112 was associated with a reduction in αSyn aggregates in the substantia nigra and improvement in motor function. Inhibition of nSMase2 thus offers a new approach to therapeutic development for neurodegenerative diseases with the potential to reduce the spread of disease-specific proteopathic proteins.

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