scholarly journals Evaluation of Daidzein Against Rotenone Induced Parkinson’s Disease and a Potential Involvement of Mitochondrial Biogenesis.

2021 ◽  
Author(s):  
Vaibhavi Peshattiwar ◽  
Suraj Muke ◽  
Aakruti Kaikini ◽  
Sneha Bagle ◽  
Vikas Dighe ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Biogenesis ◽  
Complex I ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Cardiovascular Effects ◽  
Immunohistochemical Analysis ◽  
Efficacy Evaluation

Abstract Parkinson’s disease (PD) ranks as second most prevalent neurodegenerative disorder but is devoid of neuroprotective treatment. Approaches with disease modifying ability with symptomatic relief has become an utmost necessity. Further multifactorial nature of PD presents challenges for efficacy evaluation of any potential test compound. The stated study makes an attempt to address these issues by employing a rotenone induced PD model involving a bilateral intranigral stereotactic rotenone injection for evaluation of the neuroprotective efficacy of Daidzein (DZ). DZ a soy isoflavone, is known for its various health benefits viz. immunomodulation, cardiovascular effects etc. In this study, animals after intranigral rotenone (12 μg) injection, were treated with DZ at a dose of 5, 10 and 20 mg/kg for 30 days. The neurobehavioural evaluation comprised of Rota-rod, Open field and Barnes maze test. The biochemical analysis constituting oxidative stress (Reduced glutathione, superoxide dismutase, catalase and lipid peroxidation), inflammation (TNF-α), mitochondrial alteration (complex I activity and biogenesis) was conducted on mid-brain tissue after 30 days of treatment. The SN and striatum was also subjected to immunohistochemical analysis (IHC) for TH positive neurons and Glial Fibrillary Acidic Protein. The analysis revealed significant improvement by daidzein in motor co-ordination and attenuation in cognitive deficits due to rotenone. The biochemical assessment exhibited significant decrement in oxidative stress as well as inflammation. DZ treatment also prevented complex I inhibition and promoted mitochondrial biogenesis eventually contributing to the neuroprotection apparent in IHC. Thus, the results strongly corroborate the neuroprotective potential of DZ against rotenone induced model of PD.

scholarly journals Transient Receptor Potential Channels as an Emerging Target for the Treatment of Parkinson’s Disease: An Insight Into Role of Pharmacological Interventions

2020 ◽  
Vol 8 ◽  
Author(s):  
Bhupesh Vaidya ◽  
Shyam Sunder Sharma
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Neurodegenerative Disorder ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Transient Receptor

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the symptoms of motor deficits and cognitive decline. There are a number of therapeutics available for the treatment of PD, but most of them suffer from serious side effects such as bradykinesia, dyskinesia and on-off effect. Therefore, despite the availability of these pharmacological agents, PD patients continue to have an inferior quality of life. This has warranted a need to look for alternate strategies and molecular targets. Recent evidence suggests the Transient Receptor Potential (TRP) channels could be a potential target for the management of motor and non-motor symptoms of PD. Though still in the preclinical stages, agents targeting these channels have shown immense potential in the attenuation of behavioral deficits and signaling pathways. In addition, these channels are known to be involved in the regulation of ionic homeostasis, which is disrupted in PD. Moreover, activation or inhibition of many of the TRP channels by calcium and oxidative stress has also raised the possibility of their paramount involvement in affecting the other molecular mechanisms associated with PD pathology. However, due to the paucity of information available and lack of specificity, none of these agents have gone into clinical trials for PD treatment. Considering their interaction with oxidative stress, apoptosis and excitotoxicity, TRP channels could be considered as a potential future target for the treatment of PD.

scholarly journals Effect of Curcumin on Protein Damage Induced by Rotenone in Dopaminergic PC12 Cells

2020 ◽  
Vol 21 (8) ◽  
pp. 2761 ◽  
Author(s):  
Sandra Buratta ◽  
Elisabetta Chiaradia ◽  
Alessia Tognoloni ◽  
Angela Gambelunghe ◽  
Consuelo Meschini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pc12 Cells ◽  
Cell Function ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Antioxidant Properties ◽  
Protein Damage ◽  
Substantia Nigra Pars Compacta

Oxidative stress is considered to be a key factor of the pathogenesis of Parkinson’s disease, a multifactorial neurodegenerative disorder characterized by reduced dopaminergic neurons in the substantia nigra pars compacta and accumulated protein aggregates. Rotenone is a worldwide-used pesticide that induces the most common features of Parkinson’s by direct inhibition of the mitochondrial complex I. Rotenone-induced Parkinson’s models, as well as brain tissues from Parkinson’s patients, are characterized by the presence of both lipid peroxidation and protein oxidation markers resulting from the increased level of free radical species. Oxidation introduces several modifications in protein structure, including carbonylation and nitrotyrosine formation, which severely compromise cell function. Due to the link existing between oxidative stress and Parkinson’s disease, antioxidant molecules could represent possible therapeutic tools for this disease. In this study, we evaluated the effect of curcumin, a natural compound known for its antioxidant properties, in dopaminergic PC12 cells treated with rotenone, a cell model of Parkinsonism. Our results demonstrate that the treatment of PC12 cells with rotenone causes severe protein damage, with formation of both carbonylated and nitrotyrosine-derived proteins, whereas curcumin (10 µM) co-exposure exerts protective effects by reducing the levels of oxidized proteins. Curcumin also promotes proteasome activation, abolishing the inhibitory effect exerted by rotenone on this degradative system.

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

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Samaneh Reiszadeh Jahromi ◽  
S. R. Ramesh ◽  
David I. Finkelstein ◽  
Mohammad Haddadi
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gene Mutations ◽  
Immunohistochemical Analysis ◽  
Head Capsule ◽  
Ethanol Sensitivity ◽  
Wild Type ◽  
Snca Gene ◽  
Transgenic Flies

Parkinson’s disease (PD) is an age-associated neurodegenerative condition in which some genetic variants are known to increase disease susceptibility on interaction with environmental factors inducing oxidative stress. Different mutations in the SNCA gene are reported as the major genetic contributors to PD. E46K mutation pathogenicity has not been investigated as intensive as other SNCA gene mutations including A30P and A53T. In this study, based on the GAL4-UAS binary genetic tool, transgenic Drosophila melanogaster flies expressing wild-type and E46K-mutated copies of the human SNCA gene were constructed. Western blotting, immunohistochemical analysis, and light and confocal microscopy of flies’ brains were undertaken along with the survival rate measurement, locomotor function assay, and ethanol and paraquat (PQ) tolerance to study α-synuclein neurotoxicity. Biochemical bioassays were carried out to investigate the activity of antioxidant enzymes and alterations in levels of oxidative markers following damages induced by human α-synuclein to the neurons of the transgenic flies. Overexpression of human α-synuclein in the central nervous system of these transgenic flies led to disorganized ommatidia structures and loss of dopaminergic neurons. E46K α-synuclein caused remarkable climbing defects, reduced survivorship, higher ethanol sensitivity, and increased PQ-mediated mortality. A noticeable decline in activity of catalase and superoxide dismutase enzymes besides considerable increase in the levels of lipid peroxidation and reactive oxygen species was observed in head capsule homogenates of α-synuclein-expressing flies, which indicates obvious involvement of oxidative stress as a causal factor in SNCAE46K neurotoxicity. In all the investigations, E46K copy of the SNCA gene was found to impose more severe defects when compared to wild-type SNCA. It can be concluded that the constructed Drosophila models developed PD-like symptoms that facilitate comparative studies of molecular and cellular pathways implicated in the pathogenicity of different α-synuclein mutations.

Schisandra chinensis protects against dopaminergic neuronal oxidative stress, neuroinflammation and apoptosis via BDNF/Nrf2/NF-κB pathway in 6-OHDA-induced Parkinson’s disease mice

2021 ◽  
Author(s):  
Tingxu Yan ◽  
Qianqian Mao ◽  
Xiaozhuo Zhang ◽  
Bo Wu ◽  
Kaishun Bi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Schisandra Chinensis ◽  
System Disorder

Parkinson’s disease (PD) is a progressive neurodegenerative disorder and characterized by both motor and nonmotor system disorder resulting in loss of dopaminergic (DA) neurons. Our study aimed to investigate the...

scholarly journals Toxin-Induced and Genetic Animal Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Shin Hisahara ◽  
Shun Shimohama
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Causative Factors ◽  
Genetically Determined

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. The major pathological hallmarks of PD are the selective loss of nigrostriatal dopaminergic neurons and the presence of intraneuronal aggregates termed Lewy bodies (LBs), but the pathophysiological mechanisms are not fully understood. Epidemiologically, environmental neurotoxins such as pesticides are promising candidates for causative factors of PD. Oxidative stress and mitochondrial dysfunction induced by these toxins could contribute to the progression of PD. While most cases of PD are sporadic, specific mutations in genes that cause familial forms of PD have led to provide new insights into its pathogenesis. This paper focuses on animal models of both toxin-induced and genetically determined PD that have provided significant insight for understanding this disease. We also discuss the validity, benefits, and limitations of representative models.

scholarly journals MicroRNAs, Parkinson’s Disease, and Diabetes Mellitus

2021 ◽  
Vol 22 (6) ◽  
pp. 2953
Author(s):  
Hsiuying Wang
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Cell Cycle ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Differentiation ◽  
Neurodegenerative Disorder ◽  
Glucose Absorption ◽  
Therapeutic Opportunity ◽  
The Common

Parkinson’s disease (PD) is a neurodegenerative disorder that affects 1% of the population over the age of 60. Diabetes Mellitus (DM) is a metabolic disorder that affects approximately 25% of adults over the age of 60. Recent studies showed that DM increases the risk of developing PD. The link between DM and PD has been discussed in the literature in relation to different mechanisms including mitochondrial dysfunction, oxidative stress, and protein aggregation. In this paper, we review the common microRNA (miRNA) biomarkers of both diseases. miRNAs play an important role in cell differentiation, development, the regulation of the cell cycle, and apoptosis. They are also involved in the pathology of many diseases. miRNAs can mediate the insulin pathway and glucose absorption. miRNAs can also regulate PD-related genes. Therefore, exploring the common miRNA biomarkers of both PD and DM can shed a light on how these two diseases are correlated, and targeting miRNAs is a potential therapeutic opportunity for both diseases.

scholarly journals Corrective effects of benzodiazepine derivative – diazepinone on purine and lipid metabolism in the liver of rats with Parkinson’s disease

2021 ◽  
Vol 67 (4) ◽  
pp. 64-75
Author(s):  
l.Ya. Shtanova ◽  
◽  
P.I. Yanchuk ◽  
S.P. Vesеlsky ◽  
O.V. Tsymbalyuk ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lipid Metabolism ◽  
Dopaminergic Neurons ◽  
Therapeutic Agent ◽  
Neurodegenerative Disorder ◽  
Cholesterol Esters ◽  
Layer Chromatography ◽  
Bile Samples

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra. The cause of PD is not fully understood, and effective treatments still do not exist. It is believed that oxidative stress, mitochondrial dysfunction, and impaired lipid metabolism may underlie the pathogenesis of PD. Bile contains the breakdown products of various compounds that form in hepatocytes. This study aimed to evaluate the effect of a new benzodiazepine derivative - diazepinone (DP) on purine and lipid metabolism in the liver of rats with PD caused by rotenone (ROT) by studying the composition of bile. The concentration of ATP, ADP, AMP, xanthine, hypoxanthine, phospholipids (PL), cholesterol (CHOL), cholesterol esters (ECHOL), free fatty acids (FFA), and triglycerides (TG) was quantified in bile samples by thin-layer chromatography. Our findings suggested that the ratio of AMP/ ATP in bile increased almost threefold under the influence of ROT, and with DP, it exceeded the norm by only 1.6 times. ROT also increased the content of xanthine and hypoxanthine by 28.6% and 66.7%, respectively. DP did not affect the increased xanthine content relative to control but significantly reduced the level of hypoxanthine (up to 22.2%, above normal). In addition, ROT reduced the content of bile PL, CHOL, ECHOL, TG by 23.9%, 38.6%, 47.5%, 39.2 %, respectively. Under the influence of the DP, all the above indicators returned to the level of control. Thus, diazepinone improves both the metabolism of purines and lipids in the liver of rats with ROT-simulated PD. This drug may become a therapeutic agent for treating PD and possibly other neurodegenerative diseases in the future.

scholarly journals Treating Parkinson’s disease by astrocyte reprogramming: Progress and challenges

2021 ◽  
Vol 7 (26) ◽  
pp. eabg3198
Author(s):  
Zhuang-Yao D. Wei ◽  
Ashok K. Shetty
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Symptomatic Relief ◽  
Nonmotor Symptoms ◽  
Axonal Projections ◽  
Potential Risks

Parkinson’s disease (PD), the second most prevalent neurodegenerative disorder, is typified by both motor and nonmotor symptoms. The current medications provide symptomatic relief but do not stimulate the production of new dopaminergic neurons in the substantia nigra. Astrocyte reprogramming has recently received much attention as an avenue for increasing functional dopaminergic neurons in the mouse PD brain. By targeting a microRNA (miRNA) loop, astrocytes in the mouse brain could be reprogrammed into functional dopaminergic neurons. Such in vivo astrocyte reprogramming in the mouse model of PD has successfully added new dopaminergic neurons to the substantia nigra and increased dopamine levels associated with axonal projections into the striatum. This review deliberates the astrocyte reprogramming methods using specific transcription factors and mRNAs and the progress in generating dopaminergic neurons in vivo. In addition, the translational potential, challenges, and potential risks of astrocyte reprogramming for an enduring alleviation of parkinsonian symptoms are conferred.

scholarly journals Kajian potensi antioksidan dari tanaman herbal dan pengaruhnya terhadap penyakit Parkinson

2021 ◽  
Vol 17 (1) ◽  
pp. 80-95
Author(s):  
Indri Nuraeni Pratiwi ◽  
◽  
Widhya Aligita ◽  
Marita Kaniawati ◽  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Free Radicals ◽  
Neurodegenerative Disorder ◽  
Natural Antioxidants ◽  
Muscle Stiffness ◽  
Literature Study ◽  
Neuron Damage ◽  
Herbal Plants

Background: Parkinson's disease is the most common neurodegenerative disorder affecting more than 10 million people worldwide. This disease is characterized by progressive dopaminergic neuron damage in the substantia nigra. This damage can be triggered by aging and the presence of oxidative stress because of free radicals. Antioxidants can inhibit the formation of free radicals and reduce oxidative stress, so they can be used as an alternative treatment for Parkinson's disease. Objective: This review article aimed to provide information about the antioxidant effects of selected herbal plants on Parkinson's disease. Method: This study used literature study methods sourced from national and international scientific journals published in the last 5 years (2016-2020). Literature search were carried out using databases such as Google Scholar, PubMed®, ScienceDirect, and Garuda Portal. Results: The high content of antioxidants in plants could protect nerve cells from oxidative damage and reduce symptoms such as tremors, muscle stiffness, impaired coordination and motor balance in test animals. Conclusion: Natural antioxidants from herbal plants proved to be able to prevent oxidative stress caused by free radicals and reduce symptoms of Parkinson's disease. Keywords: Parkinson's disease, antioxidants, oxidative stress, herbal plants

Sign in / Sign up

Export Citation Format

Share Document