-
Nutritional Neuroscience Jul 2023Parkinson's disease (PD) in elderly patients is the second most prevalent neurodegenerative disease. The pathogenesis of PD is associated with dopaminergic neuron...
BACKGROUND
Parkinson's disease (PD) in elderly patients is the second most prevalent neurodegenerative disease. The pathogenesis of PD is associated with dopaminergic neuron degeneration of the substantia nigra in the basal ganglia, causing classic motor symptoms. Oxidative stress, mitochondrial dysfunction, and neuroinflammation have been identified as possible pathways in laboratory investigations. Nutrition, a potentially versatile factor from all environmental factors affecting PD, has received intense research scrutiny.
METHODS
A systematic search was conducted in the MEDLINE, EMBASE, and WEB OF SCIENCE databases from 2000 until the present. Only randomized clinical trials (RCTs), observational case-control studies, and follow-up studies were included.
RESULTS
We retrieved fifty-two studies that met the inclusion criteria. Most selected studies investigated the effects of malnutrition and the Mediterranean diet (MeDiet) on PD incidence and progression. Other investigations contributed evidence on the critical role of microbiota, vitamins, polyphenols, dairy products, coffee, and alcohol intake.
CONCLUSIONS
There are still many concerns regarding the association between PD and nutrition, possibly due to underlying genetic and environmental factors. However, there is a body of evidence revealing that correcting malnutrition, gut microbiota, and following the MeDiet reduced the onset of PD and reduced clinical progression. Other factors, such as polyphenols, polyunsaturated fatty acids, and coffee intake, can have a potential protective effect. Conversely, milk and its accessory products can increase PD risk. Nutritional intervention is essential for neurologists to improve clinical outcomes and reduce the disease progression of PD.
Topics: Humans; Aged; Parkinson Disease; Coffee; Nutritional Status; Malnutrition; Polyphenols
PubMed: 35730414
DOI: 10.1080/1028415X.2022.2073107 -
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 -
Neuroscience and Biobehavioral Reviews Sep 2022Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine... (Meta-Analysis)
Meta-Analysis Review
Memory and motor deficits are commonly identified in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is transformed to MPP+ via monoamine oxidase B (MAOB), which causes oxidative stress and destroys dopaminergic (DA) neurons in substantia nigra pars compacta (SNc) and is widely used to create animal models of PD. However, to-date, a comprehensive analysis of the MPTP effects on various aspects of PD does not exist. Here, we provide a systematic review and meta-analysis on the MPTP effects on memory and motor functions by analyzing 51 studies on more than one thousand animals mainly including rats and mice. The results showed that in addition to motor functions such as coordination, balance and locomotor activity, MPTP significantly affects various mnemonic processes including spatial memory, working memory, recognition memory, and associative memory compared with the control group with some differences between systemic and intra-nigral injections on spatial memory, familiar object recognition, and anxiety-like behaviors. Nevertheless, our analysis failed to find systematic relationship between MPTP injection protocol parameters reported and the extent of the induced PD symptoms that can be a cause of concern for replicability of MPTP studies.
Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Cognition; Disease Models, Animal; Mice; Parkinson Disease; Pyrrolidines; Rats; Rodentia
PubMed: 35872230
DOI: 10.1016/j.neubiorev.2022.104792 -
Journal of Translational Medicine Sep 2023Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cell-based strategies focusing on replacement or protection of dopaminergic neurons have been considered as a potential approach to treat Parkinson's disease (PD) for decades. However, despite promising preclinical results, clinical trials on cell-therapy for PD reported mixed outcomes and a thorough synthesis of these findings is lacking. We performed a systematic review and meta-analysis to evaluate cell-therapy for PD patients.
METHODS
We systematically identified all clinical trials investigating cell- or tissue-based therapies for PD published before July 2023. Out of those, studies reporting transplantation of homogenous cells (containing one cell type) were included in meta-analysis. The mean difference or standardized mean difference in quantitative neurological scale scores before and after cell-therapy was analyzed to evaluate treatment effects.
RESULTS
The systematic literature search revealed 106 articles. Eleven studies reporting data from 11 independent trials (210 patients) were eligible for meta-analysis. Disease severity and motor function evaluation indicated beneficial effects of homogenous cell-therapy in the 'off' state at 3-, 6-, 12-, or 24-month follow-ups, and for motor function even after 36 months. Most of the patients were levodopa responders (61.6-100% in different follow-ups). Cell-therapy was also effective in improving the daily living activities in the 'off' state of PD patients. Cells from diverse sources were used and multiple transplantation modes were applied. Autografts did not improve functional outcomes, while allografts exhibited beneficial effects. Encouragingly, both transplantation into basal ganglia and to areas outside the basal ganglia were effective to reduce disease severity. Some trials reported adverse events potentially related to the surgical procedure. One confirmed and four possible cases of graft-induced dyskinesia were reported in two trials included in this meta-analysis.
CONCLUSIONS
This meta-analysis provides preliminary evidence for the beneficial effects of homogenous cell-therapy for PD, potentially to the levodopa responders. Allogeneic cells were superior to autologous cells, and the effective transplantation sites are not limited to the basal ganglia. PROSPERO registration number: CRD42022369760.
Topics: Humans; Parkinson Disease; Levodopa; Transplantation, Autologous; Transplantation, Homologous; Allogeneic Cells
PubMed: 37679754
DOI: 10.1186/s12967-023-04484-x -
Brain, Behavior, and Immunity Nov 2021There is increasing evidence highlighting the potential role of the gut-brain axis in the pathogenesis of Parkinson's disease (PD) and on the use of probiotics as a... (Review)
Review
There is increasing evidence highlighting the potential role of the gut-brain axis in the pathogenesis of Parkinson's disease (PD) and on the use of probiotics as a therapeutic strategy for this neurodegenerative disorder. While several studies have been published on the topic in recent years, there is still a lack of a comprehensive understanding of the effects of probiotics in PD and their possible underlying mechanisms. Through this systematic review, we collected a total of 17 articles, consisting of preclinical and clinical models of PD investigating the effect of probiotics on (1) energy metabolism, (2) inflammation and oxidative stress, (3) neurodegeneration, as well as (4) motor and (5) non-motor function. Articles were obtained from PubMed/Medline, Scopus, Web of Science and Embase databases. Findings from preclinical studies suggest that treatment with probiotics increases glucose metabolism (increased secretion of glucagon-like peptide-1), reduces peripheral and central inflammation (reduced interleukin-6 and tumor necrosis factor-α (TNF-α)), reduces peripheral and central oxidative stress (reduced peripheral superoxide anion levels and increased central antioxidant glutathione levels), decreases neurodegeneration (increased numbers of tyrosine hydroxylase dopaminergic neurons and levels of brain-derived neurotrophic factor), increases motor function (increased motor agility) and non-motor function (decreased memory deficits). Similarly, findings from clinical studies suggest that probiotics increase glucose metabolism (reduced insulin resistance), reduce peripheral inflammation (reduced peripheral TNF-α expression and C-reactive protein levels), and increase motor and non-motor function (decreased overall PD symptomatology and constipation); however, findings on oxidative stress were inconclusive across studies. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of probiotics on molecular and cellular mechanisms, as well as behavioural phenotypes, in either preclinical or clinical studies in PD. However, additional and more robust studies are still needed to confirm these outcomes, and should aim to focus more on bench-to-bedside approaches, in order to address the existing gaps between preclinical and clinical findings in this field.
Topics: Anti-Inflammatory Agents; Brain-Gut Axis; Dopaminergic Neurons; Humans; Parkinson Disease; Probiotics
PubMed: 34364965
DOI: 10.1016/j.bbi.2021.07.026 -
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 -
Journal of Clinical Medicine Nov 2022People with Parkinson disease suffer from a loss of dopaminergic neurons, which are involved in walking speed. Currently, virtual reality (VR) has emerged as a useful... (Review)
Review
People with Parkinson disease suffer from a loss of dopaminergic neurons, which are involved in walking speed. Currently, virtual reality (VR) has emerged as a useful tool for the rehabilitation of people with neurological diseases, optimizing results in balance and gait. This review aimed to evaluate the effectiveness of VR or video games (through face-to-face sessions and not telerehabilitation) in improving walking speed and other spatio-temporal parameters of gait, balance, and quality of life in patients with Parkinson disease. A bibliographic search was carried out in the MEDLINE, Web of Science, Scopus, and PEDro databases. This systematic review adhered to the PRISMA guideline statement and was registered in PROSPERO (CRD42020180836). From a total of 119 records, 5 studies met the inclusion criteria for qualitative analysis, of which 3 contributed to the meta-analysis; inconclusive findings were found on gait speed, balance, and quality of life after the use of non-immersive VR systems face-to-face. A greater number of studies are necessary, with a greater number of participants, to differentiate between those VR specific systems (specifically designed for rehabilitation) from commercial video games, including immersive systems, and obtain more conclusive evidence. Furthermore, it would be interesting to compare the administration of this treatment in person versus its administration via telerehabilitation, which will help plan treatment programs.
PubMed: 36431086
DOI: 10.3390/jcm11226610 -
Neurological Sciences : Official... Nov 2021Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that affects 1% of the population worldwide. Etiology of PD is likely to be... (Review)
Review
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder that affects 1% of the population worldwide. Etiology of PD is likely to be multi-factorial such as protein misfolding, mitochondrial dysfunction, oxidative stress, and neuroinflammation that contributes to the pathology of Parkinson's disease (PD), numerous studies have shown that mitochondrial dysfunction may play a key role in the dopaminergic neuronal loss. In multiple ways, the two most important are the activation of neuroinflammation and mitochondrial dysfunction, while mitochondrial dysfunction could cause neuroinflammation and vice versa. Thus, the mitochondrial proteins are the highly promising target for the development of PD. However, the limited amount of dopaminergic neurons prevented the detailed investigation of Parkinson's disease with regard to mitochondrial dysfunction. Both genetic and environmental factors are also associated with mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provide direct evidence linking mitochondrial dysfunction to PD. A decrease of mitochondrial complex I activity is observed in PD brain and in neurotoxin- or genetic factor-induced in vitro and in vivo models. Moreover, PINK1, Parkin, DJ-1 and LRRK2 mitochondrial PD gene products have important roles in mitophagy, a cellular process that clear damaged mitochondria. This review paper would discuss the evidence for the mitochondrial dysfunction and neuroinflammation in PD.
Topics: Dopaminergic Neurons; Humans; Mitochondria; Mitochondrial Proteins; Oxidative Stress; Parkinson Disease
PubMed: 34480241
DOI: 10.1007/s10072-021-05551-1 -
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