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 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 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

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 Effects of Oxidative Stress and Testosterone on Pro-Inflammatory Signaling in a Female Rat Dopaminergic Neuronal Cell Line

Endocrinology ◽  
2016 ◽  
Vol 157 (7) ◽  
pp. 2824-2835 ◽  
Author(s):  
Shaletha Holmes ◽  
Meharvan Singh ◽  
Chang Su ◽  
Rebecca L. Cunningham
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Androgen Receptor ◽  
Neurodegenerative Disorder ◽  
Dopamine Neurons ◽  
Female Rat ◽  
Stress Environment ◽  
Membrane Androgen Receptor

Parkinson's disease, a progressive neurodegenerative disorder, is associated with oxidative stress and neuroinflammation. These pathological markers can contribute to the loss of dopamine neurons in the midbrain. Interestingly, men have a 2-fold increased incidence for Parkinson's disease than women. Although the mechanisms underlying this sex difference remain elusive, we propose that the primary male sex hormone, testosterone, is involved. Our previous studies show that testosterone, through a putative membrane androgen receptor, can increase oxidative stress–induced neurotoxicity in dopamine neurons. Based on these results, this study examines the role of nuclear factor κ B (NF-κB), cyclooxygenase-2 (COX2), and apoptosis in the deleterious effects of androgens in an oxidative stress environment. We hypothesize, under oxidative stress environment, testosterone via a putative membrane androgen receptor will exacerbate oxidative stress–induced NF-κB/COX2 signaling in N27 dopaminergic neurons, leading to apoptosis. Our data show that testosterone increased the expression of COX2 and apoptosis in dopamine neurons. Inhibiting the NF-κB and COX2 pathway with CAPE and ibuprofen, respectively, blocked testosterone's negative effects on cell viability, indicating that NF-κB/COX2 cascade plays a role in the negative interaction between testosterone and oxidative stress on neuroinflammation. These data further support the role of testosterone mediating the loss of dopamine neurons under oxidative stress conditions, which may be a key mechanism contributing to the increased incidence of Parkinson's disease in men compared with women.

scholarly journals Curcumin Effectively Rescued Parkinson’s Disease-Like Phenotypes in a Novel Drosophila melanogaster Model with dUCH Knockdown

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Thi Thanh Nguyen ◽  
My Dung Vuu ◽  
Man Anh Huynh ◽  
Masamitsu Yamaguchi ◽  
Linh Thuoc Tran ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Neurodegenerative Disorder ◽  
Appropriate Therapy ◽  
Genetic And Environmental Factors ◽  
The Relationship ◽  
Common Neurodegenerative Disorder

The relationship between oxidative stress and neurodegenerative diseases has been extensively examined, and antioxidants are considered to be a promising approach for decelerating disease progression. Parkinson’s disease (PD) is a common neurodegenerative disorder and affects 1% of the population over 60 years of age. A complex combination of genetic and environmental factors contributes to the pathogenesis of PD. However, since the onset mechanisms of PD have not yet been elucidated in detail, difficulties are associated with developing effective treatments. Curcumin has been reported to have neuroprotective properties in PD models induced by neurotoxins or genetic factors such as α-synuclein, PINK1, DJ-1, and LRRK2. In the present study, we investigated the effects of curcumin in a novel Drosophila model of PD with knockdown of dUCH, a homolog of human UCH-L1. We found that dopaminergic neuron-specific knockdown of dUCH caused impaired movement and the loss of dopaminergic neurons. Furthermore, the knockdown of dUCH induced oxidative stress while curcumin decreased the ROS level induced by this knockdown. In addition, dUCH knockdown flies treated with curcumin had improved locomotive abilities and less severe neurodegeneration. Taken together, with studies on other PD models, these results strongly suggest that treatments with curcumin are an appropriate therapy for PD related to oxidative stress.

scholarly journals L-Theanine Attenuates LPS Induced Motor deficit in Experimental Rat Model of Parkinson’s Disease: Emphasis on Mitochondrial activity, Neuroinflammation and Neurotransmitters

2021 ◽  
Author(s):  
Shivam Kumar ◽  
Anupam Awasthi ◽  
Khadga Raj ◽  
Shamsher Singh
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Neurodegenerative Disorder ◽  
Dopamine Neurons ◽  
Motor Deficit ◽  
Motor Deficits ◽  
Mitochondrial Activity ◽  
Positive Effects

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the loss of dopamine neurons in the substantia nigra. The pathogenesis of PD, including oxidative stress, mitochondrial dysfunction, neuroinflammation, and neurotransmitter dysregulation. L-theanine is an amino acid found in green tea and has antioxidant, anti-inflammatory, and neuroprotective effects with a high BBB permeability. Therefore, the current study was designed to investigate the possible neuroprotective effect of L-theanine in lipopolysaccharide (LPS) induced motor deficits and striatal neurotoxicity in a rat model of PD. LPS was infused at a dose of 5 µg/5 µl PBS, stereotaxically into SNpc of rats. Treatment with L-theanine at (50 and 100 mg/kg; po), and Sinemet (36 mg/kg; po) was given from day 7 to 21 in of LPS injected rat. On a weekly basis all behavioral parameters were assessed, and animals were sacrificed on day 22. The striatum tissue of brain was isolated for biochemicals (Nitrite, GSH, catalase, SOD, mitochondrial complexes I and IV), neuroinflammatory markers (IL-1β, TNF-α, and IL-6), and neurotransmitters (serotonin, dopamine, norepinephrine, GABA, and glutamate) estimations. Results revealed that L-theanine dose-dependently and significantly reversed motor deficits, assessed through locomotor and rotarod activity. Moreover, L-theanine attenuated biochemical markers, reduced oxidative stress, and neurotransmitters dysbalance in the brain. L-theanine treatment at 100 mg/kg; po substantially reduced these pathogenic events by increasing mitochondrial activity, restoring neurotransmitter levels, and inhibiting neuroinflammation. Moreover, data suggest that the positive effects of L-theanine on motor coordination may be mediated by the suppression of nuclear factor-κB (NF-κB) induced by LPS.

scholarly journals PARK Genes Link Mitochondrial Dysfunction and Alpha-Synuclein Pathology in Sporadic Parkinson’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Wen Li ◽  
YuHong Fu ◽  
Glenda M. Halliday ◽  
Carolyn M. Sue
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disorder ◽  
Alpha Synuclein ◽  
Lewy Pathology ◽  
Age Related ◽  
Promising Therapeutic Approach ◽  
Park Genes

Parkinson’s disease (PD) is an age-related neurodegenerative disorder affecting millions of people worldwide. The disease is characterized by the progressive loss of dopaminergic neurons and spread of Lewy pathology (α-synuclein aggregates) in the brain but the pathogenesis remains elusive. PD presents substantial clinical and genetic variability. Although its complex etiology and pathogenesis has hampered the breakthrough in targeting disease modification, recent genetic tools advanced our approaches. As such, mitochondrial dysfunction has been identified as a major pathogenic hub for both familial and sporadic PD. In this review, we summarize the effect of mutations in 11 PARK genes (SNCA, PRKN, PINK1, DJ-1, LRRK2, ATP13A2, PLA2G6, FBXO7, VPS35, CHCHD2, and VPS13C) on mitochondrial function as well as their relevance in the formation of Lewy pathology. Overall, these genes play key roles in mitochondrial homeostatic control (biogenesis and mitophagy) and functions (e.g., energy production and oxidative stress), which may crosstalk with the autophagy pathway, induce proinflammatory immune responses, and increase oxidative stress that facilitate the aggregation of α-synuclein. Thus, rectifying mitochondrial dysregulation represents a promising therapeutic approach for neuroprotection in PD.

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