Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive dysfunction and loss of dopaminergic neurons of the substantia nigra pars compacta (SNc). Several pathways of programmed cell death are likely to play a role in dopaminergic neuron death, such as apoptosis, necrosis, pyroptosis and ferroptosis, as well as cell death associated with proteasomal and mitochondrial dysfunction. A better understanding of the molecular mechanisms underlying dopaminergic neuron death could inform the design of drugs that promote neuron survival. Necroptosis is a recently characterized regulated cell death mechanism that exhibits morphological features common to both apoptosis and necrosis. It requires activation of an intracellular pathway involving receptor-interacting protein 1 kinase (RIP1 kinase, RIPK1), receptor-interacting protein 3 kinase (RIP3 kinase, RIPK3) and mixed lineage kinase domain-like pseudokinase (MLKL). The potential involvement of this programmed cell death pathway in the pathogenesis of PD has been studied by analysing biomarkers for necroptosis, such as the levels and oligomerization of phosphorylated RIPK3 (pRIPK3) and phosphorylated MLKL (pMLKL), in several PD preclinical models and in PD human tissue. Although there is evidence that other types of cell death also have a role in DA neuron death, most studies support the hypothesis that this cell death mechanism is activated in PD tissues. Drugs that prevent or reduce necroptosis may provide neuroprotection for PD. In this review, we summarize the findings from these studies. We also discuss how manipulating necroptosis might open a novel therapeutic approach to reduce neuronal degeneration in PD.

Dopaminergic neuronal death via necroptosis in Parkinson's disease: A review of the literature.

Objective In this study, we used the TCGA database and ICGC database to establish a prognostic model of iron death associated with renal cell carcinoma, which can provide predictive value for the identification of iron death-related genes and clinical treatment of renal clear cell carcinoma. Methods The gene expression profiles and clinical data of renal clear cell carcinoma and normal tissues were obtained in the TCGA database and ICGC database, and the differential genes related to iron death were screened out. The differential genes were screened out by single and multifactor Cox risk regression model. R software, “edge” package (version 4.0), was used to identify the DELs of 551 transcriptional gene samples and 522 clinical samples. The risk prediction model with genes was established to analyze the correlation between the genes in the established model and clinical characteristics, Through the final screening of iron death related genes, it can be used to predict the prognosis of renal clear cell carcinoma and provide advice for clinical targeted therapy. Results Seven iron death differential genes (CLS2, FANCD2, PHKG2, ACSL3, ATP5MC3, CISD1, PEBP1) associated with renal clear cell carcinoma were finally screened and were refer to previous relevant studies. These genes are closely related to iron death and have great value for the prognosis of renal clear cell carcinoma. Conclusion Seven iron death genes can accurately predict the survival of patients with renal clear cell carcinoma.

/pdf/screening-of-differentially-expressed-iron-death-related-2pd4tf7f.pdf

Screening of Differentially Expressed Iron Death-Related Genes and the Construction of Prognosis Model in Patients with Renal Clear Cell Carcinoma

Neuronal apoptosis and neuroinflammation are key factors involved in the pathological changes of Parkinson's disease (PD). Sophoricoside (SOP) has shown anti-inflammatory and anti-apoptosis effects in various diseases. However, the role of SOP in PD has not been reported. In this experiment, we found that oral administration of SOP alleviated weight loss and motor symptoms in 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-injected mice. Further studies revealed that SOP inhibited inflammatory responses and neuronal apoptosis in the midbrain region of MPTP-injected mice. In vitro mechanistic study, we found that SOP exerts neuroprotective effects through a two-sided action. On the one hand, SOP inhibits Lipopolysaccharide (LPS)-induced inflammatory responses in microglia by inhibiting the Nuclear factor kappa-B(NF-κB) pathway. On the other hand, SOP inhibits 1-methyl-4-phenylpyridinium (MPP+)-induced neuronal apoptosis by regulating the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. Thus SOP is expected to be a potential therapeutic agent for PD by targeting neuroinflammation and neuronal apoptosis. 

Oral administration of sophoricoside (SOP) inhibits neuronal damage and neuroinflammation to curb neurodegeneration in Parkinson's disease

Abstract Aim This study aimed to investigate the mechanisms through which diosgenin inhibits the pathogenesis of non‐alcoholic fatty liver disease, focusing particularly on ferroptosis‐related pathways and its reliance on nuclear factor erythroid 2‐related factor 2 . Materials and Methods Using a rat model, we showed diosgenin's efficacy in reducing lipid deposition throughout the body and examined its impact on ferroptosis‐related gene expression in vivo . Moreover, in vitro experiments using human hepatocellular liver carcinoma cell line cells were conducted to assess oxidative stress and ferroptosis levels. Results Diosgenin decreased lipid accumulation and steatosis; lowered serum levels of total cholesterol, triglycerides, low‐density lipoprotein cholesterol, glutamic pyruvic transaminase and glutamic oxaloacetic transaminase; reduced interleukin‐1β and tumour necrosis factor‐α; diosgenin decreased malondialdehyde levels; and increased serum superoxide dismutase levels in a rat model of high‐fat diet‐induced non‐alcoholic fatty liver disease. Diosgenin upregulated the expression of nuclear factor erythroid 2‐related factor 2 and its downstream ferroptosis‐related genes to inhibit ferroptosis in the livers of rats with non‐alcoholic fatty liver disease. Diosgenin decreased reactive oxygen species levels and enhanced the expression of ferroptosis‐related genes in human hepatocellular liver carcinoma cells induced by free fatty acids, with its effects being dependent on nuclear factor erythroid 2‐related factor 2 . Conclusions This study highlights the potential of diosgenin from Dioscoreaceae plants in mitigating oxidative stress and ferroptosis levels through nuclear factor erythroid 2‐related factor 2 regulation, offering novel insights into the treatment of non‐alcoholic fatty liver disease and other metabolic disorders through traditional Chinese medicine. 

Diosgenin ameliorating non‐alcoholic fatty liver disease via <scp>Nrf2</scp>‐mediated regulation of oxidative stress and ferroptosis

Parkinson's disease (PD) is a neurodegenerative disorder triggered by the loss of dopaminergic neurons in the substantia nigra (SN). Recent studies have demonstrated that necroptosis is involved in dopaminergic neuronal cell death and the resulting neuroinflammation. During the process of necroptosis, a necrosome complex is formed consisting of the proteins receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage kinase domain-like protein (MLKL). Although the neuroprotective effects of the RIPK1-specific inhibitor necrostatin-1, as well as RIPK3 and MLKL knockout in mice, have been described, the effects of RIPK3 pharmacological inhibitors have not yet been reported in animal models of PD. In the present study, we investigated the neuroprotective effects of GSK872, a specific RIPK3 inhibitor, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. GSK872 rescued MPTP-induced motor impairment and inhibited tyrosine hydroxylase-positive dopaminergic cell death in the SN and striatum. Additionally, GSK872 inhibited the MPTP-induced increase in the expression of p-RIPK3 and p-MLKL in both the dopaminergic neurons and microglia, as assessed by biochemical and histological analyses. GSK872 further inhibited microglial activation and the expression of inflammatory mediators including NLRP3, interleukin (IL)-1β, IL-6, tumor necrosis factor-alpha, and inducible nitric oxide synthase in the SN region of MPTP mice. Using in vitro experiments, we validated the effects of GSK872 on necroptosis in SH-SY5Y neuronal and BV2 microglial cells. Overall, our results suggest that GSK872 exerts neuroprotective and anti-inflammatory effects, and may thus have therapeutic potential for PD.

Neuroprotective and anti-inflammatory effects of the RIPK3 inhibitor GSK872 in an MPTP-induced mouse model of Parkinson’s disease

Significance: There is still no cure for neurodegenerative diseases, such as Parkinson's disease (PD). Current treatments are based on the attempt to reduce dopaminergic neuronal loss, and multidis...

Cell Death-Osis of Dopaminergic Neurons and the Role of Iron in Parkinson's Disease.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of {limit} columns in the table. Remove at least 1 column to add or create another one.

Illyane Sofia Lima

Author Tools

Chat about Author

Papers

Cell Death-Osis of Dopaminergic Neurons and the Role of Iron in Parkinson's Disease.