Methylparaben protects 6-hydroxydopamine-induced neurotoxicity in SH-SY5Y cells and improved behavioral impairments in mouse model of Parkinson's disease (original) (raw)
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Neurotoxin models and treatments of Parkinson’s disease
International journal of health sciences
Parkinson’s disease (PD) is a prevalent neurological illness that manifests itself sporadically. The destruction of dopaminergic neuronal cells in the substantia nigra is the primary cause of PD. The cause of PD is unknown, while its pathogenesis is becoming to be recognized as a complex cascade of harmful elements. The majority of insights regarding PD pathogenesis reported evidence of experimental PD models, particularly those caused by neurotoxins. Although many natural and synthetic chemicals have negative effects on neuronal cells of the dopaminergic region, only a few are employed in living animal studies to mimic some of the symptoms of PD. Therefore, more studies are required to better understand the causes of PD and select better neurotoxin models in animals. In this review, we discussed the treatment drugs and animal induced model (neurotoxin model) including MPTP, rotenone,6-hydroxydopamine (6-OHDA), manganese, and paraquat for Parkinson’s disease. We also discussed the n...
Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy, 2018
6-Hydroxydopamine (6-OHDA), a synthetic neurotoxin, has been used to generate animal models of Parkinson's disease (PD). Even though 6-OHDA induced neurodegenerative model in rat, it does not reproduce all the symptoms of the disease, but it does replicate most of the cellular processes such as oxidative stress, neurodegeneration, neuroinflammation and apoptotic neuronal death. The knowledge of the mechanisms involved in neurodegeneration is relevant to define possible therapeutic targets for PD.
Experimental Animal Models of Parkinson’s Disease: A Neurotoxin Overview
Parkinson’s disease is a neurodegenerative disorder occurs due to selective degeneration of dopaminergic neurons in substantia nigra pars compacta and nigrostriatal pathways. Neurotoxins causing selective striatal/nigral degeneration of dopaminergic neurons have led us to understand the pathological aspects of Parkinson’s disease. Although the current understanding of PD pathology has significantly increased, however, the exact pathogenic mechanisms involved in PD remained elusive and so the treatments. The present review is aimed to critically discuss the neurotoxic models of PD and to provide an updated summary of the main characteristics of these model systems along with their advantages and limitations of what we believe to be the most popular PD animal models.
Journal of Neurochemistry, 2002
Abstract: 6-Hydroxydopamine (6-OHDA) is a dopaminergic neurotoxin putatively involved in the pathogenesis of Parkinson's disease (PD). Its neurotoxicity has been related to the production of reactive oxygen species. In this study we examine the effects of the antioxidants ascorbic acid (AA), glutathione (GSH), cysteine (CySH), and N-acetyl-CySH (NAC) on the autoxidation and neurotoxicity of 6-OHDA. In vitro, the autoxidation of 6-OHDA proceeds rapidly with the formation of H2O2 and with the participation of the H2O2 produced in the reaction. The presence of AA induced a reduction in the consumption of O2 during the autoxidation of 6-OHDA and a negligible presence of the p-quinone, which demonstrates the efficiency of AA to act as a redox cycling agent. The presence of GSH, CySH, and NAC produced a significant reduction in the autoxidation of 6-OHDA. In vivo, the presence of sulfhydryl antioxidants protected against neuronal degeneration in the striatum, which was particularly remarkable in the case of CySH and was attributed to its capacity to remove the H2O2 produced in the autoxidation of 6-OHDA. These results corroborate the involvement of oxidative stress as the major mechanism in the neurotoxicity of 6-OHDA and the putative role of CySH as a scavenger in relation to PD.
2001
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a preferential loss of the dopaminergic neurons of the substantia nigra pars compacta. Although the etiology of PD is unknown, major biochemical processes such as oxidative stress and mitochondrial inhibition are largely described. However, despite these findings, the actual therapeutics are essentially symptomatical and are not able to block the degenerative process. Recent histological studies performed on brains from PD patients suggest that nigral cell death could be apoptotic. However, since post-mortem studies do not allow precise determination of the sequence of events leading to this apoptotic cell death, the molecular pathways involved in this process have been essentially studied on experimental models reproducing the human disease. These latter are created by using neurotoxic compounds such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or dopamine (DA). Extensive study of these models have shown that they mimick, in vitro and in vivo, the histological and/or the biochemical characteristics of PD and thus help to define important cellular actors of cell death presumably critical for the nigral degeneration. This review reports recent data concerning the biochemical and molecular apoptotic mechanisms underlying the experimental models of PD and correlates them to the phenomena occurring in human disease.
Article, 2021
Neurodegenerative movement disorder of the central nervous system (CNS) (Parkinson’s disease [PD]) is characterized by necrosis of dopaminergic neurons in the substantia nigra pars compacta region of the midbrain. The etiology of PD is still unknown and is believed to be multifactorial, oxidative stress and mitochondrial dysfunction are widely considered major consequences, which provide important clues to the disease mechanisms. Studies have shown the role of free radicals and oxidative stress that contributes to the cascade of events leading to dopamine cell degeneration in PD. In general, in-built protective mechanisms consisting of enzymatic and non-enzymatic antioxidants in the CNS play decisive roles in preventing neuronal cell loss due to free radicals. However, the ability to produce these antioxidants decreases with aging. Therefore, antioxidant therapy alone or in combination with current treatment methods may represent an attractive strategy for treating or preventing the neurodegeneration seen in PD. Here, we summarize the recent discoveries of potential antioxidant compounds for modulating free-radical mediated oxidative stress leading to neurotoxicity in PD
NeuroToxicology, 2013
Parkinson's disease (PD) is characterized by the selective loss of dopaminergic nigrostriatal neurons, which leads to disabling motor disturbances. Sulforaphane (SFN), found in cruciferous vegetables, is a potent indirect antioxidant and recent advances have shown its neuroprotective activity in various experimental models of neurodegeneration. This study was undertaken to examine the effects of SFN on behavioral changes and dopaminergic neurotoxicity in mice exposed to 6-hydroxydopamine (6-OHDA). For this purpose, mice were treated with SFN (5 mg/kg twice a week) for four weeks after the unilateral intrastriatal injection of 6-OHDA. The increase in 6-OHDA-induced rotations and deficits in motor coordination were ameliorated significantly by SFN treatment. In addition, SFN protected 6-OHDAinduced apoptosis via blocking DNA fragmentation and caspase-3 activation. These results were further supported by immunohistochemical findings in the substantia nigra that showed that SFN protected neurons from neurotoxic effects of 6-OHDA. The neuroprotective effect of SFN may be attributed to its ability to enhance glutathione levels and its dependent enzymes (glutathione-S-transferase and glutathione reductase) and to modulate neuronal survival pathways, such as ERK1/2, in the brain of mice. These results suggest that SFN may potentially be effective in slowing down the progression of idiopathic PD by the modulation of oxidative stress and apoptotic machinery. ß
Neurotoxin-based models of Parkinson's disease
Neuroscience, 2012
Animal experimentation in the Parkinson's disease (PD) field is a classic example of how the use of animal models to study diseases can have a significant impact on human health. Among the different neurotoxin-based animal models of PD that are presently available, the 6-hydroxydopamine (6-OHDA) and the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) models have been established and validated as useful models for the development of therapeutic strategies aimed to treat motor symptoms and to study alterations of the basal ganglia that occur in this disease. The 6-OHDA rat model and the MPTP primate model have contributed enormously to translate animal experimentation into clinical practice, including pharmacological treatments and deep brain stimulation of the subthalamic nucleus. These models, along with the MPTP mouse model, are helping to elucidate the pathogenic mechanism of neurodegeneration in PD. The roles of oxidative stress, apoptosis, mitochondrial dysfunction, inflammation, and impairment of the protein degradation pathways have also come under careful consideration thanks to these models. The more recently developed paraquat and rotenone rodent models are also contributing to our understanding of neuronal cell death. However, none of the neuroprotective strategies that have worked in the pre-clinical stage have thus far been successfully translated to a clinical setting to treat PD patients. At the same time, the lack of any effective neuroprotective strategy for PD is preventing the validation of any one particular model as a screening tool for such neuroprotective strategies. Therefore, it seems that we are trapped in a vicious circle that casts doubt on the suitability of the neurotoxin-based models for this purpose. Here, we discuss how epidemiological data may help to validate a specific model with data linking a lower risk of developing PD with nutritional/consumption habits or with a specific chronic drug therapy.
Parkinson's disease (PD) is the most common disease of motor system degeneration and, after Alzheimer's disease, the second most common neurodegenerative disease. 1 Parkinson's disease takes a heavy toll in mental anguish, lost productivity, and health care expenditures. PD prominently features dopamine transmitter insufficiency, and current management is almost exclusively reliant on dopamine replacement drugs. But, while these drugs are initially effective in most patients, they do not slow the underlying degeneration in the area of the brain most affected, the substantia nigra (SN). Their effectiveness declines over time and their adverse effects become increasingly more troublesome. Broader options for long-term management are urgently needed.