α-Synuclein E46K Mutation and Involvement of Oxidative Stress in a Drosophila Model of Parkinson’s Disease

Jahromi, Samaneh Reiszadeh; Ramesh, S. R.; Finkelstein, David I.; Haddadi, Mohammad

doi:10.1155/2021/6621507

Cited by 9 publications

(9 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Studies have shown that the herbicide paraquat has neurotoxic effects ( Chaudhuri et al, 2007 ) and Drosophila models exposed to PQ are often used as the models of neurodegenerative diseases to find new neuroprotective compounds ( Jaiswal et al, 2012 ; Fernández-Hernández et al, 2016 ; Hajji et al, 2019 ). Here, Drosophila were treated with 6 mg/ml Paraquat dichloride (methyl viologen; PQ) in a sucrose solution, which provides basic energy for survival, for 24 h ( Reiszadeh Jahromi et al, 2021 ). The data showed that 6 mg/ml PQ exposure led to lethal effects in Drosophila , and the survival rate was 50%.…”

Section: Resultsmentioning

confidence: 99%

The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents

Qiang

Shi

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Stroke is the second leading cause of death worldwide and the leading cause of long-term disability that seriously endangers health and quality of human life. Tissue-type fibrinogen activator is currently the only drug approved by FDA for the treatment of ischemic stroke. Neuroprotection is theoretically a common strategy for the treatment of both ischemic and hemorrhagic stroke; therefore, the development of neuroprotective agent has been the focus of research. However, no ideal neuroprotective drug is clinically available. Phosphoglycerate kinase-1 (PGK1) activator has the effect of inhibiting apoptosis and protecting tissue damage, and therefore could be a potential neuroprotective agent. To obtain effective PGK1 activators, we virtually screened a large chemical database and their evaluated the efficacy by the Drosophila oxidative stress model, PGK1 enzymatic activity assay, and oxygen-glucose stripping reperfusion (OGD/R) model. The results showed that compounds 7979989, Z112553128 and AK-693/21087020 are potential PGK1 activators with protective effects against PQ-induced oxidative stress in the Drosophila model and could effectively ameliorate apoptosis induced by OGD/R-induced neuronal cell injury. Additionally, compounds 7979989 and Z112553128 are effective in alleviating LPS-induced cellular inflammation. This study indicated that these compounds are promising lead compounds that provide theoretical and material basis to the neuroprotective drug discovery.

show abstract

Section: Resultsmentioning

confidence: 99%

The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents

Qiang

Shi

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…PQ exposure was used in Drosophila to study PD [ 20 , 34 , 35 , 36 , 38 ]. However, the acute dose of PQ used in these models (10 or 20 mM fed to adult flies, depending on the studies) led to rapid loss of fly viability within 2–3 days, which precluded a fine analysis of the effect of PQ on αSyn protein.…”

Section: Resultsmentioning

confidence: 99%

“…PQ exposure is also commonly used to study PD in Drosophila that do not overexpress human SNCA gene [ 20 , 34 , 35 , 36 ]. In this model, fly mortality was used as proxy of PQ toxicity to identify the mechanism regulating the stress response to PQ [ 15 , 37 , 38 ]. In some studies, but not all, PQ acute exposure was also associated with the loss of dopaminergic neurons [ 37 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila

Arsac

Sedru

Dartiguelongue

et al. 2021

IJMS

View full text Add to dashboard Cite

Parkinson’s disease (PD) is characterized by the progressive accumulation of neuronal intracellular aggregates largely composed of alpha-Synuclein (αSyn) protein. The process of αSyn aggregation is induced during aging and enhanced by environmental stresses, such as the exposure to pesticides. Paraquat (PQ) is an herbicide which has been widely used in agriculture and associated with PD. PQ is known to cause an increased oxidative stress in exposed individuals but the consequences of such stress on αSyn conformation remains poorly understood. To study αSyn pathogenic modifications in response to PQ, we exposed Drosophila expressing human αSyn to a chronic PQ protocol. We first showed that PQ exposure and αSyn expression synergistically induced fly mortality. The exposure to PQ was also associated with increased levels of total and phosphorylated forms of αSyn in the Drosophila brain. Interestingly, PQ increased the detection of soluble αSyn in highly denaturating buffer but did not increase αSyn resistance to proteinase K digestion. These results suggest that PQ induces the accumulation of toxic soluble and misfolded forms of αSyn but that these toxic forms do not form fibrils or aggregates that are detected by the proteinase K assay. Collectively, our results demonstrate that Drosophila can be used to study the effect of PQ or other environmental neurotoxins on αSyn driven pathology.

show abstract

“…Furthermore, elevated 3-nitrotyrosine and nitrated alpha-synuclein immunoreactivity have been found in Parkinson’s disease patients’ Lewy bodies [ 36 ]. Intracellular peroxynitrite generation causes Alpha--synuclein aggregation [ 37 ], and oxidative damage inhibits ubiquitination and proteasome-mediated protein degradation [ 38 ]. These results demonstrate a probable relationship between oxidative damage and the production of protein aggregates that are hallmarks of Parkinson’s disease.…”

Section: Pathogenesis Of Parkinson’s Diseasementioning

confidence: 99%

Narrative Review Concerning the Clinical Spectrum of Ophthalmological Impairments in Parkinson’s Disease

Stroe

Jurja

Stuparu³

et al. 2023

Neurology International

View full text Add to dashboard Cite

Ophthalmic non-motor impairments are common in Parkinson's disease patients, from the onset of the neurodegenerative disease and even prior to the development of motor symptoms. This is a very crucial component of the potential for early detection of this disease, even in its earliest stages. Since the ophthalmological disease is extensive and impacts all extraocular and intraocular components of the optical analyzer, a competent assessment of it would be beneficial for the patients. Because the retina is an extension of the nervous system and has the same embryonic genesis as the central nervous system, it is helpful to investigate the retinal changes in Parkinson's disease in order to hypothesize insights that may also be applicable to the brain. As a consequence, the detection of these symptoms and signs may improve the medical evaluation of PD and predict the illness' prognosis. Another valuable aspect of this pathology is the fact that the ophthalmological damage contributes significantly to the decrease in the quality of life of patients with Parkinson's disease. We provide an overview of the most significant ophthalmologic impairments associated with Parkinson's disease. These results certainly constitute a large number of the prevalent visual impairments experienced by PD patients.

show abstract

α-Synuclein E46K Mutation and Involvement of Oxidative Stress in a Drosophila Model of Parkinson’s Disease

Cited by 9 publications

References 57 publications

The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents

The Discovery of Novel PGK1 Activators as Apoptotic Inhibiting and Neuroprotective Agents

Chronic Exposure to Paraquat Induces Alpha-Synuclein Pathogenic Modifications in Drosophila

Narrative Review Concerning the Clinical Spectrum of Ophthalmological Impairments in Parkinson’s Disease

Contact Info

Product

Resources

About