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 Dysfunction of mitochondria as the basis of Parkinson’s disease

2018 ◽  
Vol 6 (4) ◽  
pp. 174-181
Author(s):  
Małgorzata Popis
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Nervous System ◽  
Dopaminergic Neurons ◽  
Genetic Factors ◽  
Lewy Bodies ◽  
Main Ingredient ◽  
Mitochondrial Dynamic ◽  
Factors Affecting

AbstractParkinson's disease is the second most common neurodegenerative disease, affecting about 0,15-0,3% of the world's population. Its characteristic feature is a loss of dopaminergic neurons in the substantia nigra. PD leads to dopamine deficiency and formation of intracellular inclusions called Lewy bodies, whose main ingredient is α-synuclein. Other types of nervous system cells are also affected by changes associated with that disease. The underlying molecular pathogenesis involves multiple pathways and mechanisms: mitochondrial function, oxidative stress, genetic factors, α-synuclein proteostasis, mitochondrial dynamic impairment, and disorders of the mitophagy process. This review summarizes the factors affecting the functioning of the mitochondria and their connection to the development of Parkinson's disease.

scholarly journals Editorial for the Special Issue “Animal Models of Parkinson’s Disease and Related Disorders”

2020 ◽  
Vol 21 (12) ◽  
pp. 4250
Author(s):  
Yuzuru Imai
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Special Issue ◽  
Midbrain Dopaminergic Neurons ◽  
Age Dependent ◽  
Common Neurodegenerative Disorder

Parkinson’s disease (PD) is the second most common neurodegenerative disorder characterized by age-dependent motor dysfunction and degeneration of the midbrain dopaminergic neurons [...]

scholarly journals α-Bisabolol, a Dietary Bioactive Phytochemical Attenuates Dopaminergic Neurodegeneration through Modulation of Oxidative Stress, Neuroinflammation and Apoptosis in Rotenone-Induced Rat Model of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1421 ◽  
Author(s):  
Hayate Javed ◽  
M. F. Nagoor Meeran ◽  
Sheikh Azimullah ◽  
Lujain Bader Eddin ◽  
Vivek Dhar Dwivedi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Proinflammatory Cytokines ◽  
Rat Model ◽  
Inflammatory Mediators ◽  
Dopaminergic Neurons ◽  
Neuroprotective Effects ◽  
Dopaminergic Neurodegeneration

Rotenone (ROT), a plant-derived pesticide is a well-known environmental neurotoxin associated with causation of Parkinson’s disease (PD). ROT impairs mitochondrial dysfunction being mitochondrial complex-I (MC-1) inhibitor and perturbs antioxidant-oxidant balance that contributes to the onset and development of neuroinflammation and neurodegeneration in PD. Due to the scarcity of agents to prevent the disease or to cure or halt the progression of symptoms of PD, the focus is on exploring agents from naturally occurring dietary phytochemicals. Among numerous phytochemicals, α-Bisabolol (BSB), natural monocyclic sesquiterpene alcohol found in many ornamental flowers and edible plants garnered attention due to its potent pharmacological properties and therapeutic potential. Therefore, the present study investigated the neuroprotective effects of BSB in a rat model of ROT-induced dopaminergic neurodegeneration, a pathogenic feature of PD and underlying mechanism targeting oxidative stress, inflammation and apoptosis. BSB treatment significantly prevented ROT-induced loss of dopaminergic neurons and fibers in the substantia nigra and striatum respectively. BSB treatment also attenuated ROT-induced oxidative stress evidenced by inhibition of MDA formation and GSH depletion as well as improvement in antioxidant enzymes, SOD and catalase. BSB treatment also attenuated ROT-induced activation of the glial cells as well as the induction and release of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and inflammatory mediators (iNOS and COX-2) in the striatum. In addition to countering oxidative stress and inflammation, BSB also attenuated apoptosis of dopaminergic neurons by attenuating downregulation of anti-apoptotic protein Bcl-2 and upregulation of pro-apoptotic proteins Bax, cleaved caspases-3 and 9. Further, BSB was observed to attenuate mitochondrial dysfunction by inhibiting mitochondrial lipid peroxidation, cytochrome-C release and reinstates the levels/activity of ATP and MC-I. The findings of the study demonstrate that BSB treatment salvaged dopaminergic neurons, attenuated microglia and astrocyte activation, induction of inflammatory mediators, proinflammatory cytokines and reduced the expression of pro-apoptotic markers. The in vitro study on ABTS radical revealed the antioxidant potential of BSB. The results of the present study are clearly suggestive of the neuroprotective effects of BSB through antioxidant, anti-inflammatory and anti-apoptotic properties in ROT-induced model of PD.

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.

Neuroinflammation caused by activated microglia and astrocytes can contribute to the progression of pathogenic damage to substantia nigra neurons, playing a role in Parkinson's disease progression

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Substantia Nigra ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
High Energy ◽  
Molecular Pathways ◽  
Activated Microglia

Parkinson's disease progresses by a number of regionally specific cellular and molecular mechanisms. Furthermore, these pathways interact and have an influence on one another in both normal and pathological conditions. Neuroinflammation caused by activated microglia and astrocytes can contribute to the progression of pathogenic damage to substantia nigra (SN) neurons. Similarly, oxidative stress may be caused by a variety of stressors, such as contaminants in the environment or age-related mitochondrial dysfunction, leading to the production of reactive oxygen species (ROS). Dopamine auto-oxidation is a significant generator of ROS in dopaminergic neurons, resulting in neuronal oxidative stress. The high energy demands of dopaminergic neurons may result in mitochondrial dysfunction and oxidative damage as they age. Because mitophagy clears dysfunctional mitochondria from SN neurons, mutation-related abnormalities in autophagy of defective proteins might allow damaging proteins to accumulate in the cell. Because the effects of aging on these molecular pathways and cellular activities are unknown, further study into these molecular pathways and their connections in normal and sick states will be essential for developing disease-specific therapies.

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 Dopamine Oxidation and Autophagy

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Patricia Muñoz ◽  
Sandro Huenchuguala ◽  
Irmgard Paris ◽  
Juan Segura-Aguilar
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Protein Degradation ◽  
Dopaminergic Neurons ◽  
Molecular Mechanisms ◽  
Neurodegenerative Process ◽  
Dopamine Oxidation

The molecular mechanisms involved in the neurodegenerative process of Parkinson's disease remain unclear. Currently, there is a general agreement that mitochondrial dysfunction,α-synuclein aggregation, oxidative stress, neuroinflammation, and impaired protein degradation are involved in the neurodegeneration of dopaminergic neurons containing neuromelanin in Parkinson's disease. Aminochrome has been proposed to play an essential role in the degeneration of dopaminergic neurons containing neuromelanin by inducing mitochondrial dysfunction, oxidative stress, the formation of neurotoxicα-synuclein protofibrils, and impaired protein degradation. Here, we discuss the relationship between the oxidation of dopamine to aminochrome, the precursor of neuromelanin, autophagy dysfunction in dopaminergic neurons containing neuromelanin, and the role of dopamine oxidation to aminochrome in autophagy dysfunction in dopaminergic neurons. Aminochrome induces the following: (i) the formation ofα-synuclein protofibrils that inactivate chaperone-mediated autophagy; (ii) the formation of adducts withα- andβ-tubulin, which induce the aggregation of the microtubules required for the fusion of autophagy vacuoles and lysosomes.

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.

scholarly journals Mitochondrial Dysfunction andα-Synuclein Synaptic Pathology in Parkinson’s Disease: Who’s on First?

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Michela Zaltieri ◽  
Francesca Longhena ◽  
Marina Pizzi ◽  
Cristina Missale ◽  
PierFranco Spano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Dopaminergic Neurons ◽  
Lewy Bodies ◽  
Nigrostriatal System ◽  
Primary Role ◽  
Lewy Neurites ◽  
Synaptic Pathology ◽  
Lines Of Evidence

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder. Its characteristic neuropathological features encompass the loss of dopaminergic neurons of the nigrostriatal system and the presence of Lewy bodies and Lewy neurites. These are intraneuronal and intraneuritic proteinaceous insoluble aggregates whose main constituent is the synaptic proteinα-synuclein. Compelling lines of evidence indicate that mitochondrial dysfunction andα-synuclein synaptic deposition may play a primary role in the onset of this disorder. However, it is not yet clear which of these events may come first in the sequel of processes leading to neurodegeneration. Here, we reviewed data supporting either thatα-synuclein synaptic deposition precedes and indirectly triggers mitochondrial damage or that mitochondrial deficits lead to neuronal dysfunction andα-synuclein synaptic accumulation. The present overview shows that it is still difficult to establish the exact temporal sequence and contribution of these events to PD.

scholarly journals Effect of Nebivolol on MPTP Induced Parkinson’s Disease in Mice

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Karthigadevi. K ◽  
Anbazhagan. S ◽  
Jajjara Gopi Sudheer Kumar ◽  
Kavimani. S
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Parkinson Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Blocking Agent ◽  
Protective Effects ◽  
The Brain ◽  
Anti Inflammation

Parkinson’s disease is the major neurodegenerative disorder, which is due to the loss of dopaminergic neurons in the brain and results in bradykinesia, rigidity, tremor and instable posture. Oxidative stress, Inflammation, Apoptosis has been implicated in the molecular etiopathogenesis of Parkinson disease. In the present study, Nebivolol, a Cardioselective ?-blocking agent which is also reported as an antioxidant, anti-inflammation, anticonvulsant, inhibition of apoptosis and protective effects on gastric ulcer. Hence, nebivolol has been tested for its antiparkinson activity against 1-Methyl, 4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) induced model of Parkinson disease in mice. From this study, the result shown that the nebivolol exerts its beneficial effect against MPTP induced Parkinson’s disease by virtue of its antioxidative, anti-inflammatory and by increases the Dopamine levels in the brain.

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