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Neural Regeneration Research Jul 2024Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may...
Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, and although restoring striatal dopamine levels may improve symptoms, no treatment can cure or reverse the disease itself. Stem cell therapy has a regenerative effect and is being actively studied as a candidate for the treatment of Parkinson's disease. Mesenchymal stem cells are considered a promising option due to fewer ethical concerns, a lower risk of immune rejection, and a lower risk of teratogenicity. We performed a meta-analysis to evaluate the therapeutic effects of mesenchymal stem cells and their derivatives on motor function, memory, and preservation of dopaminergic neurons in a Parkinson's disease animal model. We searched bibliographic databases (PubMed/MEDLINE, Embase, CENTRAL, Scopus, and Web of Science) to identify articles and included only peer-reviewed in vivo interventional animal studies published in any language through June 28, 2023. The study utilized the random-effect model to estimate the 95% confidence intervals (CI) of the standard mean differences (SMD) between the treatment and control groups. We use the systematic review center for laboratory animal experimentation's risk of bias tool and the collaborative approach to meta-analysis and review of animal studies checklist for study quality assessment. A total of 33 studies with data from 840 Parkinson's disease model animals were included in the meta-analysis. Treatment with mesenchymal stem cells significantly improved motor function as assessed by the amphetamine-induced rotational test. Among the stem cell types, the bone marrow MSCs with neurotrophic factor group showed largest effect size (SMD [95% CI] = -6.21 [-9.50 to -2.93], P = 0.0001, I2 = 0.0 %). The stem cell treatment group had significantly more tyrosine hydroxylase positive dopaminergic neurons in the striatum ([95% CI] = 1.04 [0.59 to 1.49], P = 0.0001, I2 = 65.1 %) and substantia nigra (SMD [95% CI] = 1.38 [0.89 to 1.87], P = 0.0001, I2 = 75.3 %), indicating a protective effect on dopaminergic neurons. Subgroup analysis of the amphetamine-induced rotation test showed a significant reduction only in the intracranial-striatum route (SMD [95% CI] = -2.59 [-3.25 to -1.94], P = 0.0001, I2 = 74.4 %). The memory test showed significant improvement only in the intravenous route (SMD [95% CI] = 4.80 [1.84 to 7.76], P = 0.027, I2 = 79.6 %). Mesenchymal stem cells have been shown to positively impact motor function and memory function and protect dopaminergic neurons in preclinical models of Parkinson's disease. Further research is required to determine the optimal stem cell types, modifications, transplanted cell numbers, and delivery methods for these protocols.
PubMed: 38051903
DOI: 10.4103/1673-5374.387976 -
International Journal of Molecular... Sep 2022Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies... (Review)
Review
Parkinson's disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
Topics: Biomarkers; Dopamine; Dopaminergic Neurons; Extracellular Vesicles; Humans; MicroRNAs; Parkinson Disease; Proteomics; RNA, Long Noncoding; alpha-Synuclein
PubMed: 36232833
DOI: 10.3390/ijms231911508 -
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 -
Frontiers in Aging Neuroscience 2020Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models...
Bone marrow stromal cells (BMSCs) has been reported to have beneficial effects in improving behavioral deficits, and rescuing dopaminergic neuron loss in rodent models of Parkinson's disease (PD). However, their pooled effects for dopaminergic neuron have yet to be described. To review the neuroprotective effect of naïve BMSCs in rodent models of PD. The PubMed, EMBASE, and Web of Science databases were searched up to September 30, 2020. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified BMSCs; (3) comparison: not specified; (4) primary outcome: tyrosine hydroxylase level in the substantia nigra pars compacta and rotational behavior; secondary outcome: rotarod test, and limb function; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis. Twenty-seven animal studies were included. The median quality score was 4.7 (interquartile range, 2-8). Overall standardized mean difference between animals treated with naïve BMSCs and controls was 2.79 (95% confidence interval: 1.70, 3.87; < 0.001) for densitometry of tyrosine hydroxylase-positive staining; -1.54 (95% confidence interval: -2.11, -0.98; < 0.001) for rotational behavior. Significant heterogeneity among studies was observed. Results of this meta-analysis suggest that naïve BMSCs therapy increased dopaminergic neurons and ameliorated behavioral deficits in rodent models of PD.
PubMed: 33362527
DOI: 10.3389/fnagi.2020.539933