scholarly journals Physiological and Pathological Role of Alpha-synuclein in Parkinson’s Disease Through Iron Mediated Oxidative Stress; The Role of a Putative Iron-responsive Element

2009 ◽  
Vol 10 (3) ◽  
pp. 1226-1260 ◽  
Author(s):  
David Olivares ◽  
Xudong Huang ◽  
Lars Branden ◽  
Nigel Greig ◽  
Jack Rogers
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Iron Responsive Element ◽  
Responsive Element

scholarly journals Differential effects of loss of park7 activity on Iron Responsive Element (IRE) gene sets: Implications for the role of iron dyshomeostasis in the pathophysiology of Parkinson’s disease

2021 ◽  
Author(s):  
Hui Yung Chin ◽  
Michael Lardelli ◽  
Lyndsey Collins-Praino ◽  
Karissa Barthelson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Function ◽  
Bioinformatic Analysis ◽  
Untranslated Regions ◽  
Iron Responsive Element ◽  
Gene Sets ◽  
Oxidative Phosphorylation Pathway ◽  
Responsive Element

AbstractMutation of the gene PARK7 (DJ1) causes monogenic autosomal recessive Parkinson’s disease (PD) in humans. Subsequent alterations of PARK7 protein function lead to mitochondrial dysfunction, a major element in PD pathology. Homozygous mutants for the PARK7-orthologous genes in zebrafish, park7, show changes to gene expression in the oxidative phosphorylation pathway, supporting that disruption of energy production is a key feature of neurodegeneration in PD. Iron is critical for normal mitochondrial function, and we have previously used bioinformatic analysis of IRE-bearing transcripts in brain transcriptomes to find evidence supporting the existence of iron dyshomeostasis in Alzheimer’s disease. Here, we analysed IRE-bearing transcripts in the transcriptome data from homozygous park7−/− mutant zebrafish brains. We found that the set of genes with “high quality” IREs in their 5’ untranslated regions (UTRs, the HQ5’IRE gene set) was significantly altered in these 4-month-old park7−/− brains. However, sets of genes with IREs in their 3’ UTRs appeared unaffected. The effects on HQ5’IRE genes are possibly driven by iron dyshomeostasis and/or oxidative stress, but illuminate the existence of currently unknown mechanisms with differential overall effects on 5’ and 3’ IREs.

scholarly journals Modeling of Parkinson's disease on D. melanogaster: oxidative stress and the role of isogenization of transgenic lines

2018 ◽  
Vol 22 ◽  
pp. 46-50
Author(s):  
Kh. A. Dronska ◽  
Kh. M. Yavdyk ◽  
O. H. Stasyk ◽  
N. P. Matiytsiv
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Alpha Synuclein ◽  
Dopamine Neurons ◽  
Significant Difference ◽  
Before And After ◽  
Transgenic Lines ◽  
Stress Susceptibility

Aim. Oxidative stress (OS) is considered one of the main factors that leads to the degeneration of dopamine neurons in Parkinson's disease (PD). The purpose of the work was to test sensitivity to the conditions of the OS of D. melanogaster individuals with expression of human alpha-synuclein in neurons UAS-SNCA/elavGal4; and establish the role of the isogenization of the lines derived from stock collections in the study of this phenotype. Methods. For the isogenyzation of the line, we conducted five generations of sequential crossings of individuals with insertion of human alpha synuclein gene into the w1118 line. A 4-day test using H2O2 as prooxidant was used to test the sensitivity to OS conditions. Results. Individuals with expression of alpha-synuclein gene in neurons were characterized by statistically significant sensitivity to OS conditions, compared with controls. Also, there was a significant difference in the degree of sensitivity to the OS in the second day of the experiment in individuals before and after the isogenization of the effector line. Conclusions. Hypersensitivity to the OS is detected as a specific phenotype under conditions of expression of human alpha-synuclein in Drosophila neurons. The importance of the isogenization of transgenic lines for the characterization of the stress susceptibility phenotype is established.Keywords: Drosophila melanogaster, alpha-synuclein, oxidative stress, isogenization.

scholarly journals Loss of park7 activity has differential effects on expression of iron responsive element (IRE) gene sets in the brain transcriptome in a zebrafish model of Parkinson’s disease

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Hui Yung Chin ◽  
Michael Lardelli ◽  
Lyndsey Collins-Praino ◽  
Karissa Barthelson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protein Function ◽  
Bioinformatic Analysis ◽  
Zebrafish Model ◽  
Iron Responsive Element ◽  
Brain Transcriptome ◽  
Gene Sets ◽  
Oxidative Phosphorylation Pathway ◽  
Responsive Element

AbstractMutation of the gene PARK7 (DJ1) causes monogenic autosomal recessive Parkinson’s disease (PD) in humans. Subsequent alterations of PARK7 protein function lead to mitochondrial dysfunction, a major element in PD pathology. Homozygous mutants for the PARK7-orthologous genes in zebrafish, park7, show changes to gene expression in the oxidative phosphorylation pathway, supporting that disruption of energy production is a key feature of neurodegeneration in PD. Iron is critical for normal mitochondrial function, and we have previously used bioinformatic analysis of IRE-bearing transcripts in brain transcriptomes to find evidence supporting the existence of iron dyshomeostasis in Alzheimer’s disease. Here, we analysed IRE-bearing transcripts in the transcriptome data from homozygous park7−/− mutant zebrafish brains. We found that the set of genes with “high quality” IREs in their 5′ untranslated regions (UTRs, the HQ5′IRE gene set) was significantly altered in these 4-month-old park7−/− brains. However, sets of genes with IREs in their 3′ UTRs appeared unaffected. The effects on HQ5′IRE genes are possibly driven by iron dyshomeostasis and/or oxidative stress, but illuminate the existence of currently unknown mechanisms with differential overall effects on 5′ and 3′ IREs.

Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽  
2015 ◽  
Vol 5 (95) ◽  
pp. 77706-77715 ◽  
Author(s):  
Supinder Kaur ◽  
Aamir Nazir
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Caenorhabditis Elegans ◽  
Potential Role ◽  
Alpha Synuclein ◽  
C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

scholarly journals Potential Role of Epigenetic Mechanism in Manganese Induced Neurotoxicity

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
Prashant Tarale ◽  
Tapan Chakrabarti ◽  
Saravanadevi Sivanesan ◽  
Pravin Naoghare ◽  
Amit Bafana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dna Methyltransferase ◽  
Apoptotic Cell ◽  
Genetic Difference ◽  
Epigenetic Mechanism ◽  
Dna Hypomethylation ◽  
Manganese Neurotoxicity

Manganese is a vital nutrient and is maintained at an optimal level (2.5–5 mg/day) in human body. Chronic exposure to manganese is associated with neurotoxicity and correlated with the development of various neurological disorders such as Parkinson’s disease. Oxidative stress mediated apoptotic cell death has been well established mechanism in manganese induced toxicity. Oxidative stress has a potential to alter the epigenetic mechanism of gene regulation. Epigenetic insight of manganese neurotoxicity in context of its correlation with the development of parkinsonism is poorly understood. Parkinson’s disease is characterized by theα-synuclein aggregation in the form of Lewy bodies in neuronal cells. Recent findings illustrate that manganese can cause overexpression ofα-synuclein.α-Synuclein acts epigenetically via interaction with histone proteins in regulating apoptosis.α-Synuclein also causes global DNA hypomethylation through sequestration of DNA methyltransferase in cytoplasm. An individual genetic difference may also have an influence on epigenetic susceptibility to manganese neurotoxicity and the development of Parkinson’s disease. This review presents the current state of findings in relation to role of epigenetic mechanism in manganese induced neurotoxicity, with a special emphasis on the development of Parkinson’s disease.

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