In vivo, in vitro and pharmacologic models of Parkinson's disease

Freezing Of Gait ◽

Motor Symptoms ◽

Symptomatic Management ◽

Parkinson's disease (PD), which is the second most common neurodegenerative disorder after Alzheimer's disease, is firstly defined after James Parkinson's report. It carries motor symptoms such as resting tremor, bradykinesia and rigidity of skeletal muscle and freezing of gait. Furthermore, non-motor symptoms such as cognitive and behavioral problems, besides sensory impairments are seen in the patients. However, they may also suffer from sleep disorders or autonomic dysfunction. Although there are some medications in order to symptomatic management, but unfortunately, scientist could not have found exact approaches to cure this disease. Hence, producing a model which can express the most pathophysiologic and behavioral aspects of the disease is a desire. In this paper, we aimed to describe the different models of Parkinson's disease in brief.

Protective effects of saffron and its constituent crocetin to motor symptoms, short life span and rough-eyed phenotypes in the fly models of Parkinson’s disease in vivo

10.1101/2020.12.06.408997 ◽

2020 ◽

Author(s):

Eiji Inoue ◽

Takahiro Suzuki ◽

Yasuharu Shimizu ◽

Keiichi Sudo ◽

Haruhisa Kawasaki ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Life Span ◽

Neuronal Cell ◽

Crocus Sativus ◽

Motor Symptoms ◽

Protective Effects

AbstractParkinson’s disease (PD) is a common neurodegenerative disorder with motor symptoms linked to the loss of dopaminergic neurons in the brain. α-Synuclein is an aggregation-prone neural protein that plays a role in the pathogenesis of PD. In our previous paper, we found that saffron; the stigma of Crocus sativus Linné (Iridaceae), and its constituents (crocin and crocetin) suppressed aggregation of α-synuclein and promoted the dissociation of α-synuclein fibrils in vitro. In this study, we investigated the effect of dietary saffron and its constituent, crocetin, in vivo on a fly PD model overexpressing several mutant α-synuclein in a tissue-specific manner. Saffron and crocetin significantly suppressed the decrease of climbing ability in the Drosophila overexpressing A30P (A30P fly PD model) or G51D (G51D fly PD model) mutated α-synuclein in neurons. Saffron and crocetin extended the life span in the G51D fly PD model. Saffron suppressed the rough-eyed phenotype and the dispersion of the size histogram of the ocular long axis in A30P fly PD model in eye. Saffron had a cytoprotective effect on a human neuronal cell line with α-synuclein fibrils. These data showed that saffron and its constituent crocetin have protective effects on the progression of PD disease in animals in vivo and suggest that saffron and crocetin can be used to treat PD.

Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation

Microbial Cell Factories ◽

10.1186/s12934-021-01589-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Xiao-yi Kuai ◽

Xiao-han Yao ◽

Li-juan Xu ◽

Yu-qing Zhou ◽

Li-ping Zhang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rating Scale ◽

Fecal Microbiota Transplantation ◽

Fecal Microbiota ◽

Motor Symptoms ◽

Gastrointestinal Dysfunction ◽

Before And After ◽

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.

Effect of Harmine against Parkinson’s Disease Protein (PARK7) through Molecular Docking Studies

International Journal for Research in Applied Science and Engineering Technology ◽

10.22214/ijraset.2021.36192 ◽

2021 ◽

Vol 9 (VI) ◽

pp. 5479-5485

Author(s):

Love Kumar

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Molecular Docking ◽

Docking Studies ◽

In Vivo Studies ◽

Receptor Protein ◽

Unknown Etiology

Parkinson’s disease (PD) is a common known neurodegenerative disorder with unknown etiology. It was estimated about 0.3% prevalence in the U.S population and enhance to 4 to 5% in older than 85 years. All studies were depending on the molecular docking where all ligands and protein PARK7 (PDB ID: 2RK3) were interacted by docked process. Some natural compounds was selected such as Harmine, Alloxan, Alpha spinasterol, Myrcene, and Vasicinone and PARK7 (PDB ID: 2RK3) protein. According to the PyRx and SWISS ADME result, Harmine was the only ligand which was showing minimum binding affinity. AutoDock Vina software was used for docking process between ligand (Harmine) and receptor protein PARK7 (PDB ID: 2RK3). The result was visualized under PyMol. Harmine was inhibiting the activity of PARK7 (PDB ID: 2RK3) and it may be used for the treatment of PD in future prospect after its in vitro and in vivo studies.

Swallowing dysfunctions in Parkinson’s disease patients: a novel challenge for the internist

Italian Journal of Medicine ◽

10.4081/itjm.2019.1117 ◽

2019 ◽

Vol 13 (2) ◽

pp. 91-94 ◽

Cited By ~ 1

Author(s):

Elena Barbagelata ◽

Antonello Nicolini ◽

Paola Tognetti

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Practice ◽

Aspiration Pneumonia ◽

Movement Pattern ◽

Morbidity And Mortality ◽

Motor Symptoms ◽

Common Causes ◽

Parkinson’s disease (PD) is a chronic neurodegenerative disorder with a typical movement pattern, as well as different, less studied non-motor symptoms such as dysphagia. Disease-related disorders in efficacy or safety in the process of swallowing usually lead to malnutrition, dehydration or pneumonia. Dysphagia and subsequent aspiration pneumonia are common causes of morbidity and mortality in those with PD. The aim of this review is to identify and evaluate the existing literature on swallowing disorders in PD and providing recommendations for clinical practice routine.

A Possible Novel Anti-Inflammatory Mechanism for the Pharmacological Prolyl Hydroxylase Inhibitor 3,4-Dihydroxybenzoate: Implications for Use as a Therapeutic for Parkinson’s Disease

Parkinson s Disease ◽

10.1155/2012/364684 ◽

2012 ◽

Vol 2012 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Shankar J. Chinta ◽

Subramanian Rajagopalan ◽

Abirami Ganesan ◽

Julie K. Andersen

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Microglial Activation ◽

Nitrosative Stress ◽

Oxidative And Nitrosative Stress ◽

Prolyl Hydroxylases ◽

Age Related

Parkinson’s disease (PD) is an age-related neurodegenerative disorder characterized in part by the preferential loss of nigrostriatal dopaminergic neurons. Although the precise etiology of PD is unknown, accumulating evidence suggests that PD involves microglial activation that exerts neurotoxic effects through production of proinflammatory cytokines and increased oxidative and nitrosative stress. Thus, controlling microglial activation has been suggested as a therapeutic target for combating PD. Previously we demonstrated that pharmacological inhibition of a class of enzymes known as prolyl hydroxylases via 3,4-dihydroxybenzoate administration protected against MPTP-induced neurotoxicity, however the exact mechanisms involved were not elucidated. Here we show that this may be due to DHB’s ability to inhibit microglial activation. DHB significantly attenuated LPS-mediated induction of nitric oxide synthase and pro-inflammatory cytokines in murine BV2 microglial cellsin vitroin conjunction with reduced ROS production and activation of NFκB and MAPK pathways possibly due to up-regulation of HO-1 levels. HO-1 inhibition partially abrogates LPS-mediated NFκB activity and subsequent NO induction.In vivo, DHB pre-treatment suppresses microglial activation elicited by MPTP treatment. Our results suggest that DHB’s neuroprotective properties could be due to its ability to dampen induction of microglial activation via induction of HO-1.

A clinical-anatomical signature of Parkinson’s Disease identified with partial least squares and magnetic resonance imaging

10.1101/168989 ◽

2017 ◽

Cited By ~ 3

Author(s):

Yashar Zeighami ◽

Seyed-Mohammad Fereshtehnejad ◽

Mahsa Dadar ◽

D. Louis Collins ◽

Ronald B. Postuma ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Least Squares ◽

Partial Least Squares ◽

Large Scale ◽

De Novo ◽

Clinical Manifestations ◽

Motor Symptoms ◽

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by a wide array of motor and non-motor symptoms. It remains unclear whether neurodegeneration in discrete loci gives rise to discrete symptoms, or whether network-wide atrophy gives rise to the unique behavioural and clinical profile associated with PD. Here we apply a data-driven strategy to isolate large-scale, multivariate associations between distributed atrophy patterns and clinical phenotypes in PD. In a sample of N = 229 de novo PD patients, we estimate disease-related atrophy using deformation based morphometry (DBM) of T1 weighted MR images. Using partial least squares (PLS), we identify a network of subcortical and cortical regions whose collective atrophy is associated with a clinical phenotype encompassing motor and non-motor features. Despite the relatively early stage of the disease in the sample, the atrophy pattern encompassed lower brainstem, substantia nigra, basal ganglia and cortical areas, consistent with the Braak hypothesis. In addition, individual variation in this putative atrophy network predicted longitudinal clinical progression in both motor and non-motor symptoms. Altogether, these results demonstrate a pleiotropic mapping between neurodegeneration and the clinical manifestations of PD, and that this mapping can be detected even in de novo patients.

Doença de Parkinson: Revisão Clínica e Atualização

Acta Médica Portuguesa ◽

10.20344/amp.11978 ◽

2019 ◽

Vol 32 (10) ◽

pp. 661

Author(s):

Verónica Cabreira ◽

João Massano

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Clinical Findings ◽

Disease Biomarkers ◽

The Past ◽

Non Motor Symptoms ◽

Deep Brain

Parkinson’s disease is the second most common neurodegenerative disorder, and a significant increase in its prevalence in the past three decades has been documented. Environmental and genetic factors contribute to the pathophysiology of this disease, and 5% – 10% of cases have a monogenic cause. The diagnosis relies on clinical findings, supported by adequate testing. There is no absolute method to diagnose Parkinson’s disease in vivo, except for genetic testing in specific circumstances, whose usefulness is limited to a minority of cases. New diagnostic criteria have been recently proposed with the aim of improving diagnostic accuracy, emphasizing findings that might point to other causes of parkinsonism. The available therapeutic options are clinically useful, as they improve the symptoms as well as the quality of life of patients. After the introduction of levodopa, deep brain stimulation emerged as the second therapy with an important symptomatic impact in the treatment of Parkinson’s disease. Non-motor symptoms and motor complications are responsible for a large proportion of disability, so these should be identified and treated. Current scientific research is focused on the identification of disease biomarkers allowing correct and timely diagnosis, and on creating more effective therapies, thus fulfilling current clinical unmet needs. This paper presents an updated review on Parkinson’s disease, guiding the readership through current concepts, and allowing their application to daily clinical practice.

Dietary Factors in the Etiology of Parkinson’s Disease

BioMed Research International ◽

10.1155/2015/672838 ◽

2015 ◽

Vol 2015 ◽

pp. 1-16 ◽

Cited By ~ 39

Author(s):

Zeynep S. Agim ◽

Jason R. Cannon

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Neurological Diseases ◽

Epidemiological Studies ◽

Dietary Factors ◽

Calorie Intake ◽

Cooked Meat

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The majority of cases do not arise from purely genetic factors, implicating an important role of environmental factors in disease pathogenesis. Well-established environmental toxins important in PD include pesticides, herbicides, and heavy metals. However, many toxicants linked to PD and used in animal models are rarely encountered. In this context, other factors such as dietary components may represent daily exposures and have gained attention as disease modifiers. Severalin vitro, in vivo, and human epidemiological studies have found a variety of dietary factors that modify PD risk. Here, we critically review findings on association between dietary factors, including vitamins, flavonoids, calorie intake, caffeine, alcohol, and metals consumed via food and fatty acids and PD. We have also discussed key data on heterocyclic amines that are produced in high-temperature cooked meat, which is a new emerging field in the assessment of dietary factors in neurological diseases. While more research is clearly needed, significant evidence exists that specific dietary factors can modify PD risk.

Association of fall risk factors and non-motor symptoms in patients with early Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-84720-w ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kyum-Yil Kwon ◽

Suyeon Park ◽

Eun Ji Lee ◽

Mina Lee ◽

Hyunjin Ju

Keyword(s):

Risk Factors ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Freezing Of Gait ◽

Prior History ◽

Motor Symptoms ◽

Related Factors ◽

Related Risk ◽

History Of ◽

AbstractThe association of non-motor symptoms (NMSs) with fall-related factors in patients with Parkinson’s disease (PD) remains to be further elucidated in the early stages of the disease. Eighty-six patients with less than 5 years of the onset of PD were retrospectively enrolled in the study. We assessed potential fall-related risk factors including (1) a history of falls during the past year (faller versus non-faller), (2) the fear of falling (FoF), and (3) the freezing of gait (FoG). Different types of NMSs were measured using the Montreal Cognitive Assessment (MoCA), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Parkinson’s disease Fatigue Scale (PFS), and the Scales for Outcomes in Parkinson’s disease—Autonomic dysfunction (SCOPA-AUT). The faller group (37.2%) showed higher scores for BDI, BAI, PFS, and SCOPA-AUT, compared to the non-faller group. From logistic regression analyses, the prior history of falls was related to the gastrointestinal domain of SCOPA-AUT, FoF was associated with BAI, and gastrointestinal and urinary domains of SCOPA-AUT, and FoG was linked to BAI and gastrointestinal domain of SCOPA-AUT. In conclusion, we found that fall-related risk factors in patients with early PD were highly connected with gastrointestinal dysautonomia.

Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson’s Disease In Vitro and In Vivo

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/8169125 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Hefeng Zhou ◽

Min Shao ◽

Xuanjun Yang ◽

Chuwen Li ◽

Guozhen Cui ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Motor Coordination ◽

Nerve Fibers ◽

Substantia Nigra Pars Compacta ◽

Neuroprotective Effects ◽

6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer’s disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.