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Cureus Sep 2021Parkinson's disease (PD), a neurodegenerative disorder, is caused due to the loss of dopaminergic neurons in substantia nigra pars compacta, and it mainly affects the... (Review)
Review
Parkinson's disease (PD), a neurodegenerative disorder, is caused due to the loss of dopaminergic neurons in substantia nigra pars compacta, and it mainly affects the motor function of the diseased individual. The most effective treatment for PD to date is levodopa, the precursor molecule for dopamine which ultimately helps overcome the loss of dopamine in the brain. However, long-term levodopa therapy significantly impairs patients' quality of life by causing various disabling motor and non-motor complications. We conducted this study intending to review the available literature that has compared the efficacy and safety of continuous subcutaneous apomorphine infusion (CSAI) with other available treatment options like deep brain stimulation, intestinal levodopa gel, and oral dopaminergic agents. We searched PubMed, Embase, and Scopus databases using the appropriate search strategy. The studies which compared the safety and efficacy of continuous subcutaneous apomorphine infusion to other available treatment options in advanced Parkinson's disease were included in our study. The bias assessment of the studies was done using Cochrane Risk of Bias 2.0 tool for randomized controlled trials, Risk of Bias In Non-Randomized Studies - of Interventions (ROBINS-I) tool for non-randomized interventional studies, and Joanna Briggs Institute Critical Appraisal tools (JBI) for cohort studies. We included eight articles in our systematic review including a randomized controlled trial. None of the included studies had a high risk of bias. We found that in patients with advanced Parkinson's, CSAI demonstrated definite improvement in off-time duration. CSAI has also been shown to improve various non-motor functions, including neuropsychiatric problems in these patients. CSAI has demonstrated safety and efficacy in patients with advanced Parkinson's disease. However, the decision-making is multifactorial. Hence, further studies are required that directly compare the available treatment options with one another and study their overall effects on patients' quality of life.
PubMed: 34660137
DOI: 10.7759/cureus.17949 -
Cureus Aug 2021Parkinson's disease (PD) is a neurodegenerative disease caused due to the destruction of dopaminergic neurons and the deposition of α-synuclein proteins, known as Lewy... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative disease caused due to the destruction of dopaminergic neurons and the deposition of α-synuclein proteins, known as Lewy bodies. Generally, the diagnosis of PD is centered around motor symptoms. However, the early recognition of non-motor symptoms such as autonomic dysfunction, sleep disturbances, and cognitive and psychiatric disturbances are gaining increased attention for the early diagnosis of PD. Rapid eye movement (REM) sleep behavior disorder or REM sleep behavior disorder (RBD) is described as parasomnia, which is a condition of loss of normal muscle atonia causing the person to act out vivid dreams and it has been seen to be associated with the misprocessing of intercellular α-synuclein leading to neurodegenerative diseases such as PD. This review's objective is to highlight the significance of RBD as a prodromal premotor marker for the early detection of PD. We used PubMed as our primary database to search for articles on May 2, 2021, and a total of 1849 articles were found in our initial search using keywords and medical subject heading (MeSH) keywords. Thereafter, we removed the duplicates, applied the inclusion/exclusion criteria, and did a quality appraisal to include 10 articles in this study. We concluded that the recognition and diagnosis of RBD are of paramount importance to detect early PD, and further longitudinal studies and clinical trials are of utmost importance to understand their correlation; also, treatment trials are needed to prevent the phenoconversion of RBD into PD.
PubMed: 34522507
DOI: 10.7759/cureus.17026 -
International Journal of Molecular... Aug 2021Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these...
Neonicotinoids are a class of insecticides that exert their effect through a specific action on neuronal nicotinic acetylcholine receptors (nAChRs). The success of these insecticides is due to this mechanism of action, since they act as potent agonists of insect nAChRs, presenting low affinity for vertebrate nAChRs, which reduces potential toxic risk and increases safety for non-target species. However, although neonicotinoids are considered safe, their presence in the environment could increase the risk of exposure and toxicity. On the other hand, although neonicotinoids have low affinity for mammalian nAChRs, the large quantity, variety, and ubiquity of these receptors, combined with its diversity of functions, raises the question of what effects these insecticides can produce in non-target species. In the present systematic review, we investigate the available evidence on the biochemical and behavioral effects of neonicotinoids on the mammalian nervous system. In general, exposure to neonicotinoids at an early age alters the correct neuronal development, with decreases in neurogenesis and alterations in migration, and induces neuroinflammation. In adulthood, neonicotinoids induce neurobehavioral toxicity, these effects being associated with their modulating action on nAChRs, with consequent neurochemical alterations. These alterations include decreased expression of nAChRs, modifications in acetylcholinesterase activity, and significant changes in the function of the nigrostriatal dopaminergic system. All these effects can lead to the activation of a series of intracellular signaling pathways that generate oxidative stress, neuroinflammation and, finally, neuronal death. Neonicotinoid-induced changes in nAChR function could be responsible for most of the effects observed in the different studies.
Topics: Animals; Humans; Insecticides; Mammals; Neonicotinoids; Neurons; Receptors, Nicotinic
PubMed: 34445117
DOI: 10.3390/ijms22168413 -
Clinical Parkinsonism & Related... 2021Smooth pursuit eye movement (SPEM) abnormalities are commonly seen in Parkinson's disease (PD). Both reduced speed and saccades seen during SPEM, also known as saccadic... (Review)
Review
Smooth pursuit eye movement (SPEM) abnormalities are commonly seen in Parkinson's disease (PD). Both reduced speed and saccades seen during SPEM, also known as saccadic pursuit (SP), have been studied in PD. A comprehensive literature review analyzed 26 studies of SPEM and PD. It appears that a greater proportion of PD patients have SPEM abnormalities consisting of reduced SPEM gain and/or SP compared to the normal population. It is not clear whether SPEM abnormalities are present early in the disease or begin sometime during disease progression. SPEM abnormalities may be correlated with disease severity but do not fluctuate or respond to dopaminergic medication in the same manner as other motor symptoms in PD. SPEM in PD is composed of normal SPEM interspersed with SP composed of both catch up and anticipatory saccades. This differs from other neurodegenerative disorders and may be related to an inability to inhibit extraneous saccades or to increased distraction reflecting executive dysfunction. Because the basal ganglia are involved in SPEM physiology, degeneration of the SNr neurons in PD may explain abnormal SPEM in this disorder. Since dementia, aging and medication effects influence SPEM, they should be controlled for in future studies of SPEM in PD. SP is easily detected on clinical exam and may be a biomarker for the disease or for disease progression. Oculomotor testing can be an important part of the Parkinson's exam.
PubMed: 34316663
DOI: 10.1016/j.prdoa.2020.100085 -
Journal of Parkinson's Disease 2021The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The hallmark of Parkinson's disease is depletion of dopamine in the basal ganglia. Models of Parkinson's disease include dopamine as a contributor to disease progression. However, intraneuronal levels of dopamine have not been reported.
OBJECTIVE
Meta-analytic methods were utilized to determine intracellular dopamine levels in Parkinson's disease.
METHODS
A systematic review of the literature and frequentist meta-analyses were performed. Dopamine levels were scaled for cell and axon numbers as well as VMAT2 protein levels.
RESULTS
Reduced tissue dopamine, dopaminergic cell bodies and VMAT2 protein were confirmed. The ratio of Parkinson's to normal brain intracellular dopamine scaled for either cell or axon number, each with VMAT2 level in the caudate ranged from 1.49 to 1.87 (p = 0.51 and p = 0.12, respectively) and in the putamen from 0.75 to 4.61 (p = 0.40 and 0.001, respectively).
CONCLUSION
Free, intracellular dopamine levels are not reduced in Parkinson's disease compared to normals to a similar degree as are total tissue concentrations, supporting the relevance of modulating VMAT2, neuromelanin and/or dopamine synthesis as rational neuroprotective strategies.
Topics: Basal Ganglia; Dopamine; Dopaminergic Neurons; Humans; Parkinson Disease; Putamen
PubMed: 34024786
DOI: 10.3233/JPD-212715 -
Frontiers in Pharmacology 2021Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor... (Review)
Review
Parkinson's disease (PD) is a common neurodegenerative disease featured by progressive degeneration of nigrostriatal dopaminergic neurons (DA) accompanied with motor function impairment. Accumulating evidence has demonstrated that natural compounds from herbs have potent anti-PD efficacy in PD models. Among those compounds, resveratrol, a polyphenol found in many common plants and fruits, is more effective against PD. Resveratrol has displayed a potent neuroprotective efficacy in several PD animal models. However, there is still no systematic analysis of the quality of methodological design of these studies, nor of their results. In this review, we retrieved and analyzed 18 studies describing the therapeutic effect of resveratrol on PD animal models. There are 5 main kinds of PD rodent models involved in the 18 articles, including chemical-induced (MPTP, rotenone, 6-OHDA, paraquat, and maneb) and transgenic PD models. The neuroprotective mechanisms of resveratrol were mainly concentrated on the antioxidation, anti-inflammation, ameliorating mitochondrial dysfunction, and motor function. We discussed the disadvantages of different PD animal models, and we used meta-analysis approach to evaluate the results of the selected studies and used SYRCLE's risk of bias tool to evaluate the methodological quality. Our analytical approach minimized the bias of different studies. We have also summarized the pharmacological mechanisms of resveratrol on PD models as reported by the researchers. The results of this study support the notion that resveratrol has significant neuroprotective effects on different PD models quantified using qualitative and quantitative methods. The collective information in our review can guide researchers to further plan their future experiments without any hassle regarding preclinical and clinical studies. In addition, this collective assessment of animal studies can provide a qualitative analysis of different PD animal models, either to guide further testing of these models or to avoid unnecessary duplication in their future research.
PubMed: 33967780
DOI: 10.3389/fphar.2021.644219 -
Current Neuropharmacology 2022Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by a significant decrease in dopamine levels, caused by progressive...
Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by a significant decrease in dopamine levels, caused by progressive degeneration of the dopaminergic neurons in the nigrostriatal pathway. Multiple mechanisms have been implicated in its pathogenesis, including oxidative stress, neuroinflammation, protein aggregation, mitochondrial dysfunction, insufficient support for neurotrophic factors and cell apoptosis. The absence of treatments capable of slowing or stopping the progression of PD has increased the interest in the natural antioxidant substances present in the diet, since they have multiple beneficial properties and it is possible that they can influence the mechanisms responsible for the dysfunction and death of dopaminergic neurons. Thus, the purpose of this systematic review is to analyze the results obtained in a set of studies carried out in the last years, which describe the neuroprotective, antioxidant and regenerative functions of some naturally occurring antioxidants in experimental models of PD. The results show that the exogenous no enzymatic antioxidants can significantly modify the biochemical and behavioral mechanisms that contribute to the pathophysiology of Parkinsonism in experimental animals. Therefore, it is possible that they may contribute to effective neuroprotection by providing a significant improvement in neuropathological markers. In conclusion, the results of this review suggest that exogenous antioxidants can be promising therapeutic candidates for the prevention and treatment of PD.
Topics: Animals; Antioxidants; Disease Models, Animal; Dopamine; Neurodegenerative Diseases; Neuroprotective Agents; Parkinson Disease
PubMed: 33882808
DOI: 10.2174/1570159X19666210421092725 -
Experimental and Therapeutic Medicine Jun 2021Previous studies have reported that ginsenoside-Rg1 (G-Rg1) was able to mitigate the loss of dopaminergic neurons in animal models of Parkinson's disease (PD). The...
Previous studies have reported that ginsenoside-Rg1 (G-Rg1) was able to mitigate the loss of dopaminergic neurons in animal models of Parkinson's disease (PD). The present study provided a systematic review and meta-analysis of preclinical studies to pool current evidence on the effect of G-Rg1 on neurogenesis in the treatment of PD. Eligible studies were identified through a search from six databases: PubMed, EMBASE, Web of Science, VIP, Chinese National Knowledge Infrastructure and the Wanfang database. Primary outcomes were tyrosine hydroxylase (TH)-positive cells in the nigra, Nissl staining-positive cells in the nigra, pole test time and dopamine (DA) levels in the striatum. A total of 18 eligible studies were identified, involving 343 animals. Of these, 13 reported a significant relationship between G-Rg1 and improved TH-positive cells in the nigra compared with the control group (P<0.00001). Furthermore, 3 studies reported a significant relationship between G-Rg1 and improved Nissl-positive cells in the nigra compared with the control group (P<0.00001). In addition, 4 studies reported a significant effect of G-Rg1 to reduce the total pole test time compared with that in the control group (P=0.001). A total of 3 studies indicated a significant association between G-Rg1 and improved DA levels in the striatum compared with the control group (P<0.00001). These results suggested that G-Rg1 has positive effects in attenuating damage in models of PD, and thus, it is a potential candidate neuroprotective drug for human PD.
PubMed: 33850524
DOI: 10.3892/etm.2021.9984 -
International Immunopharmacology Jun 2021Parkinson's disease is a progressive neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Neuroinflammation,...
Parkinson's disease is a progressive neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Neuroinflammation, another hallmark of the disease, is thought to play an important role in the neurodegenerative process. While mitigating neuroinflammation could prove beneficial for Parkinson's disease, identifying the most relevant biological processes and pharmacological targets as well as drugs to modulate them remains highly challenging. The present study aimed to better understand the protein network behind neuroinflammation in Parkinson's disease and to prioritize possible targets for its pharmacological modulation. We first used text-mining to systematically collect the proteins significantly associated to Parkinson's disease neuroinflammation over the scientific literature. The functional interaction network formed by these proteins was then analyzed by integrating functional enrichment, network topology analysis and drug-protein interaction analysis. We identified 57 proteins significantly associated to neuroinflammation in Parkinson's disease. Toll-like Receptor Cascades as well as Interleukin 4, Interleukin 10 and Interleukin 13 signaling appeared as the most significantly enriched biological processes. Protein network analysis using STRING and CentiScaPe identified 8 proteins with the highest ability to control these biological processes underlying neuroinflammation, namely caspase 1, heme oxygenase 1, interleukin 1beta, interleukin 4, interleukin 6, interleukin 10, tumor necrosis factor alpha and toll-like receptor 4. These key proteins were indexed to be targetable by a total of 38 drugs including 27 small compounds 11 protein-based therapies. In conclusion, our study highlights key proteins in Parkinson's disease neuroinflammation as well as pharmacological compounds acting on them. As such, it may facilitate the prioritization of biomarkers for the development of diagnostic, target-engagement assessment and therapeutic tools against Parkinson's disease.
Topics: Animals; Brain; Humans; Inflammation; Parkinson Disease; Protein Interaction Maps
PubMed: 33756233
DOI: 10.1016/j.intimp.2021.107526 -
Frontiers in Neural Circuits 2021The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex...
The globus pallidus externa (GPe) functions as a central hub in the basal ganglia for processing motor and non-motor information through the creation of complex connections with the other basal ganglia nuclei and brain regions. Recently, with the adoption of sophisticated genetic tools, substantial advances have been made in understanding the distinct molecular, anatomical, electrophysiological, and functional properties of GPe neurons and non-neuronal cells. Impairments in dopamine transmission in the basal ganglia contribute to Parkinson's disease (PD), the most common movement disorder that severely affects the patients' life quality. Altered GPe neuron activity and synaptic connections have also been found in both PD patients and pre-clinical models. In this review, we will summarize the main findings on the composition, connectivity and functionality of different GPe cell populations and the potential GPe-related mechanisms of PD symptoms to better understand the cell type and circuit-specific roles of GPe in both normal and PD conditions.
Topics: Basal Ganglia; Dopamine; Globus Pallidus; Humans; Neurons; Parkinson Disease
PubMed: 33737869
DOI: 10.3389/fncir.2021.645287