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Frontiers in Aging Neuroscience 2022Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of...
Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by neuroinflammation, formation of Lewy bodies, and progressive loss of dopaminergic neurons in the substantia nigra of the brain. In this review, we summarize evidence obtained by animal studies demonstrating neuroinflammation as one of the central pathogenetic mechanisms of PD. We also focus on the protein factors that initiate the development of PD and other neurodegenerative diseases. Our targeted literature search identified 40 pre-clinical and studies written in English. Nuclear factor B (NF-kB) pathway is demonstrated as a common mechanism engaged by neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6hydroxydopamine (6-OHDA), as well as the bacterial lipopolysaccharide (LPS). The α-synuclein protein, which plays a prominent role in PD neuropathology, may also contribute to neuroinflammation by activating mast cells. Meanwhile, 6-OHDA models of PD identify microsomal prostaglandin E synthase-1 (mPGES-1) as one of the contributors to neuroinflammatory processes in this model. Immune responses are used by the central nervous system to fight and remove pathogens; however, hyperactivated and prolonged immune responses can lead to a harmful neuroinflammatory state, which is one of the key mechanisms in the pathogenesis of PD.
PubMed: 35912090
DOI: 10.3389/fnagi.2022.855776 -
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 -
Applied Neuropsychology. Adult Apr 2024Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by motor symptoms that initially manifest unilaterally. Whilst some studies indicate that... (Review)
Review
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by motor symptoms that initially manifest unilaterally. Whilst some studies indicate that right-side onset is associated with greater symptom severity, others report no differences between right-side and left-side onset patients. The present meta-analysis was thus designed to reconcile inconsistencies in the literature and determine whether side of onset affects PD symptom severity. Following the PRISMA guidelines 1013 studies were initially identified in database and grey literature searches; following title and abstract, and full text, screening 34 studies met the stringent inclusion criteria ( = 2210). Results of the random-effects meta-analysis indicated no difference in symptom severity between PD patients with left-side ( = 1104) and right-side ( = 1106) onset. As such, the meta-analysis suggests that the side of onset should not be used to predict symptom trajectory or to formulate prognoses for PD patients. The current meta-analysis was the first to focus on the relationship between the side of onset and symptom severity in PD. However, the studies included were limited by the common exclusion of left-handed participants. Future research would benefit from exploring other factors that may influence symptom severity and disease progression in PD, such as asymmetric loss of nigrostriatal dopaminergic neurons.
PubMed: 38640454
DOI: 10.1080/23279095.2024.2338803 -
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 -
Journal of Medical Engineering &... Oct 2021Nowadays, there are several diseases which affect different systems of the body, producing changes in the correct functioning of the organism and the people lifestyles....
Nowadays, there are several diseases which affect different systems of the body, producing changes in the correct functioning of the organism and the people lifestyles. One of them is Parkinson's disease (PD), which is defined as a neurodegenerative disorder provoked by the destruction of dopaminergic neurons in the brain, resulting in a set of motor and non-motor symptoms. As this disease affects principally to ancient people, several researchers have studied different treatments and therapies for stopping neurodegeneration and diminishing symptoms, to improve the quality patients' lives. The most common therapies created for PD are based on pharmacological treatment for controlling the degeneration advance and the physical ones which do not reveal the progress of patients. For this reason, this review paper opens the possibility for using wearable motion capture systems as an option for the control and study of PD. Therefore, it aims to (1) study the different wearable systems used for capture the movements of PD patients and (2) determine which of them bring better results for monitoring and assess PD people. For the analysis, it uses papers based on experiments that prove the functioning of several motion systems in different aspects as monitoring, treatment and diagnose of the disease. As a result, it works with 30 papers which describe the factors mentioned before. Additionally, the paper uses journals and literature review about the pathology, its characteristics and the function of wearable sensors for the correct understanding of the topic.
Topics: Brain; Humans; Motion; Movement; Parkinson Disease; Wearable Electronic Devices
PubMed: 34060967
DOI: 10.1080/03091902.2021.1922528 -
Neurological Sciences : Official... May 2020Parkinson's disease (PD) is the second most prevalent neurodegenerative disease characterized by severe dyskinesia due to a progressive loss of dopaminergic neurons...
Parkinson's disease (PD) is the second most prevalent neurodegenerative disease characterized by severe dyskinesia due to a progressive loss of dopaminergic neurons along the nigro-striatal pathway. The current focus of treatment is to relieve symptoms through administration of levodopa, such as L-3,4-dihydroxy phenylalanine replacement therapy, dopaminergic agonist administration, functional neurosurgery, and gene therapy, rather than preventing dopaminergic neuronal damage. Hence, the application and development of neuroprotective/disease modification strategies is absolutely necessary. Currently, stem cell therapy has been considered for PD treatment. As for the stem cells, mesenchymal stem cells (MSCs) seem to be the most promising. In this review, we analyze the mechanisms of action of MSCs in Parkinson's disease, including growth factor secretion, exocytosis, and attenuation of neuroinflammation. To determine efficacy and protect patients from possible adverse effects, ongoing rigorous and controlled studies of MSC treatment will be critical.
Topics: Animals; Brain; Clinical Trials as Topic; Humans; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neurons; Parkinson Disease; Treatment Outcome
PubMed: 31919699
DOI: 10.1007/s10072-020-04240-9 -
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 -
Journal of Toxicology and Environmental... May 2023Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that results in a decrease in dopamine...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra that results in a decrease in dopamine levels, resulting in motor-type disturbances. Different vertebrate models, such as rodents and fish, have been used to study PD. In recent decades, (zebrafish) has emerged as a potential model for the investigation of neurodegenerative diseases due to its homology to the nervous system of humans. In this context, this systematic review aimed to identify publications that reported the utilization of neurotoxins as an experimental model of parkinsonism in zebrafish embryos and larvae. Ultimately, 56 articles were identified by searching three databases (PubMed, Web of Science, and Google Scholar). Seventeen studies using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 4 1-methyl-4-phenylpyridinium (MPP+), 24 6-hydroxydopamine (6-OHDA), 6 paraquat/diquat, 2 rotenone, and 6 articles using other types of unusual neurotoxins to induce PD were selected. Neurobehavioral function, such as motor activity, dopaminergic neuron markers, oxidative stress biomarkers, and other relevant parameters in the zebrafish embryo-larval model were examined. In summary, this review provides information to help researchers determine which chemical model is suitable to study experimental parkinsonism, according to the effects induced by neurotoxins in zebrafish embryos and larvae.
Topics: Humans; Animals; Neurotoxins; Zebrafish; Parkinson Disease; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Larva; Parkinsonian Disorders; Neurodegenerative Diseases; Models, Theoretical; Disease Models, Animal
PubMed: 36859813
DOI: 10.1080/10937404.2023.2182390 -
Acta Neuropsychiatrica Feb 2021Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and...
OBJECTIVE
Vitamin D deficiency may be a clinical problem in patients with addictions. The authors systematically searched for studies addressing vitamin D and addiction and develop a hypothesis which can direct future research of the possible mechanistic role of vitamin D in the process of addiction.
METHODS
Systematic review of the literature found in PubMed and EMBASE followed by narrative review combined with clinical experiences leading to hypotheses for future research.
RESULTS
Only five articles were identified about a role of vitamin D in the pathophysiology of addiction. Their results are in line with a possible influence of vitamin D in dopaminergic transmission. The cerebral vitamin D status depends on the functionality of genetic variants of vitamin D receptor and other involved genes. Routine serum calcidiol levels may not adequately reflect cerebral vitamin D status. Uncertainty exists regarding appropriate calcidiol blood levels and proper dosages for affecting the central nervous system (CNS).
CONCLUSIONS
The putative pathophysiological role of vitamin D in substance abuse has been insufficiently studied which calls to more studies how to measure cerebral vitamin D status in clinical practice. Research is indicated whether vitamin D supplementation should use higher dosages and aim to reach higher calcidiol serum levels. Measuring dopaminergic functioning within the prefrontal cortex as reflected by neuropsychological tests selected as suitable could be a appropriate proxy for the cerebral vitamin D status when studying the pharmacogenomics of this functionality in patients.
Topics: Adult; Alcoholism; Animals; Behavior, Addictive; Calcifediol; Central Nervous System; Dopaminergic Neurons; Female; Humans; Male; Middle Aged; Models, Animal; Pharmacogenetics; Polymorphism, Single Nucleotide; Rats; Receptors, Calcitriol; Vitamin D; Vitamin D Deficiency
PubMed: 33183376
DOI: 10.1017/neu.2020.41 -
Basic & Clinical Pharmacology &... Jul 2024Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and...
Parkinson's disease (PD) is a neurodegenerative disease that affects dopaminergic neurons, thus impairing dopaminergic signalling. Quercetin (QUE) has antioxidant and neuroprotective properties that are promising for the treatment of PD. This systematic review aimed to investigate the therapeutic effects of QUE against PD in preclinical models. The systematic search was performed in PubMed, Scopus and Web of Science. At the final screening stage, 26 articles were selected according to pre-established criteria. Selected studies used different methods for PD induction, as well as animal models. Most studies used rats (73.08%) and mice (23.08%), with 6-OHDA as the main strategy for PD induction (38.6%), followed by rotenone (30.8%). QUE was tested immersed in oil, nanosystems or in free formulations, in varied routes of administration and doses, ranging from 10 to 400 mg/kg and from 5 to 200 mg/kg in oral and intraperitoneal administrations, respectively. Overall, evidence from published data suggests a potential use of QUE as a treatment for PD, mainly through the inhibition of oxidative stress, neuroinflammatory response and apoptotic pathways.
Topics: Animals; Humans; Mice; Rats; Antioxidants; Apoptosis; Disease Models, Animal; Neuroprotective Agents; Oxidative Stress; Oxidopamine; Parkinson Disease; Parkinsonian Disorders; Quercetin; Rotenone
PubMed: 38682342
DOI: 10.1111/bcpt.14011