scholarly journals The Endotoxin-Induced Neuroinflammation Model of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-25 ◽  
Author(s):  
Kemal Ugur Tufekci ◽  
Sermin Genc ◽  
Kursad Genc
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Experimental Studies ◽  
Bacterial Endotoxin ◽  
Dopaminergic Neurodegeneration ◽  
Nigrostriatal Dopaminergic Neurodegeneration ◽  
Peripheral Immune Cells

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. Although the exact cause of the dopaminergic neurodegeneration remains elusive, recent postmortem and experimental studies have revealed an essential role for neuroinflammation that is initiated and driven by activated microglial and infiltrated peripheral immune cells and their neurotoxic products (such as proinflammatory cytokines, reactive oxygen species, and nitric oxide) in the pathogenesis of PD. A bacterial endotoxin-based experimental model of PD has been established, representing a purely inflammation-driven animal model for the induction of nigrostriatal dopaminergic neurodegeneration. This model, by itself or together with genetic and toxin-based animal models, provides an important tool to delineate the precise mechanisms of neuroinflammation-mediated dopaminergic neuron loss. Here, we review the characteristics of this model and the contribution of neuroinflammatory processes, induced by thein vivoadministration of bacterial endotoxin, to neurodegeneration. Furthermore, we summarize the recent experimental therapeutic strategies targeting endotoxin-induced neuroinflammation to elicit neuroprotection in the nigrostriatal dopaminergic system. The potential of the endotoxin-based PD model in the development of an early-stage specific diagnostic biomarker is also emphasized.

scholarly journals Plasma-borne indicators of inflammasome activity in Parkinson’s disease patients

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Faith L. Anderson ◽  
Katharine M. von Herrmann ◽  
Angeline S. Andrew ◽  
Yuliya I. Kuras ◽  
Alison L. Young ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Nlrp3 Inflammasome ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Inflammasome Activation ◽  
Membrane Pore ◽  
Related Proteins ◽  
Inflammasome Activity

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms and loss of dopaminergic neurons of the substantia nigra. Inflammation and cell death are recognized aspects of PD suggesting that strategies to monitor and modify these processes may improve the management of the disease. Inflammasomes are pro-inflammatory intracellular pattern recognition complexes that couple these processes. The NLRP3 inflammasome responds to sterile triggers to initiate pro-inflammatory processes characterized by maturation of inflammatory cytokines, cytoplasmic membrane pore formation, vesicular shedding, and if unresolved, pyroptotic cell death. Histologic analysis of tissues from PD patients and individuals with nigral cell loss but no diagnosis of PD identified elevated expression of inflammasome-related proteins and activation-related “speck” formation in degenerating mesencephalic tissues compared with controls. Based on previous reports of circulating inflammasome proteins in patients suffering from heritable syndromes caused by hyper-activation of the NLRP3 inflammasome, we evaluated PD patient plasma for evidence of inflammasome activity. Multiple circulating inflammasome proteins were detected almost exclusively in extracellular vesicles indicative of ongoing inflammasome activation and pyroptosis. Analysis of plasma obtained from a multi-center cohort identified elevated plasma-borne NLRP3 associated with PD status. Our findings are consistent with others indicating inflammasome activity in neurodegenerative disorders. Findings suggest mesencephalic inflammasome protein expression as a histopathologic marker of early-stage nigral degeneration and suggest plasma-borne inflammasome-related proteins as a potentially useful class of biomarkers for patient stratification and the detection and monitoring of inflammation in PD.

Olfactory Function and Diffusion Tensor Imaging as Markers of Mild Cognitive Impairment in Early Stages of Parkinson's Disease

2021 ◽  
pp. 155005942110582
Author(s):  
Sophie A. Stewart ◽  
Laura Pimer ◽  
John D. Fisk ◽  
Benjamin Rusak ◽  
Ron A. Leslie ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Impairment ◽  
Diffusion Tensor Imaging ◽  
Mild Cognitive Impairment ◽  
White Matter ◽  
Neurodegenerative Disorder ◽  
Diffusion Tensor ◽  
Early Stage ◽  
White Matter Integrity

Parkinson's disease (PD) is a neurodegenerative disorder that is typified by motor signs and symptoms but can also lead to significant cognitive impairment and dementia Parkinson's Disease Dementia (PDD). While dementia is considered a nonmotor feature of PD that typically occurs later, individuals with PD may experience mild cognitive impairment (PD-MCI) earlier in the disease course. Olfactory deficit (OD) is considered another nonmotor symptom of PD and often presents even before the motor signs and diagnosis of PD. We examined potential links among cognitive impairment, olfactory functioning, and white matter integrity of olfactory brain regions in persons with early-stage PD. Cognitive tests were used to established groups with PD-MCI and with normal cognition (PD-NC). Olfactory functioning was examined using the University of Pennsylvania Smell Identification Test (UPSIT) while the white matter integrity of the anterior olfactory structures (AOS) was examined using magnetic resonance imaging (MRI) diffusion tensor imaging (DTI) analysis. Those with PD-MCI demonstrated poorer olfactory functioning and abnormalities based on all DTI parameters in the AOS, relative to PD-NC individuals. OD and microstructural changes in the AOS of individuals with PD may serve as additional biological markers of PD-MCI.

scholarly journals 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

2020 ◽  
Author(s):  
Eiji Inoue ◽  
Takahiro Suzuki ◽  
Yasuharu Shimizu ◽  
Keiichi Sudo ◽  
Haruhisa Kawasaki ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Life Span ◽  
Neurodegenerative Disorder ◽  
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.

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

2021 ◽  
Vol 9 (VI) ◽  
pp. 5479-5485
Author(s):  
Love Kumar
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Neurodegenerative Disorder ◽  
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.

scholarly journals 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

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Shankar J. Chinta ◽  
Subramanian Rajagopalan ◽  
Abirami Ganesan ◽  
Julie K. Andersen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Microglial Activation ◽  
Nitrosative Stress ◽  
Neurodegenerative Disorder ◽  
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.

scholarly journals A minimally invasive catheter-based ultrasound technology for therapeutic interventions in brain: initial preclinical studies

2018 ◽  
Vol 44 (2) ◽  
pp. E13 ◽  
Author(s):  
Goutam Ghoshal ◽  
Lucy Gee ◽  
Tamas Heffter ◽  
Emery Williams ◽  
Corinne Bromfield ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Minimally Invasive ◽  
Focused Ultrasound ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Rodent Model ◽  
Therapeutic Interventions ◽  
Porcine Liver

OBJECTIVEMinimally invasive procedures may allow surgeons to avoid conventional open surgical procedures for certain neurological disorders. This paper describes the iterative process for development of a catheter-based ultrasound thermal therapy applicator.METHODSUsing an ultrasound applicator with an array of longitudinally stacked and angularly sectored tubular transducers within a catheter, the authors conducted experimental studies in porcine liver, in vivo and ex vivo, in order to characterize the device performance and lesion patterns. In addition, they applied the technique in a rodent model of Parkinson’s disease to investigate the feasibility of its application in brain.RESULTSThermal lesions with multiple shapes and sizes were readily achieved in porcine liver. The feasibility of catheter-based focused ultrasound in the treatment of brain conditions was demonstrated in a rodent model of Parkinson’s disease.CONCLUSIONSThe authors show proof of principle of a catheter-based ultrasound system that can create lesions with concurrent thermode-based measurements.

scholarly journals The development of visual neuroimaging research of acupuncture in the treatment of Parkinson’s disease

2019 ◽  
Vol 5 (3) ◽  
pp. 161-168 ◽  
Author(s):  
Yuan Yang ◽  
Suhua Miao ◽  
Rongsong Zhou ◽  
Yu Ma ◽  
Yuqi Zhang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neuronal Activity ◽  
Structural Changes ◽  
Neurodegenerative Disorder ◽  
Cerebral Metabolism ◽  
Experimental Studies ◽  
Brain Regions ◽  
Imaging Studies ◽  
Surgical Treatments

Parkinson’s disease (PD) is a progressive neurodegenerative disorder commonly observed in middle-aged and elderly. Currently, its etiology and pathogenesis are still not completely understood. It is associated with many symptoms that severely affect patients’ health and quality of life. At present, the PD clinical treatment mainly aimed to alleviate symptoms, and both medicinal and surgical treatments have side effects and treatment blind spots. The use of acupuncture for the treatment of PD is relatively widespread, and its safety and efficacy have been gradually accepted by the public and medical professions. However, the efficacy of acupuncture in experimental studies remains controversial. Therefore, this paper reviews imaging studies on the use of acupuncture for the treatment of PD. From the study, it shows that acupuncture can improve the neuronal activity, activate the neuronal activity in damaged brain regions, affect relevant neural networks and brain circulation, improve cerebral metabolism, and cause structural changes in related brain regions. Intuitive and visible imaging studies provide objective bases on the use of acupuncture for the treatment of PD.

Gender and Age Difference in Clinical Features and severity of Parkinson’s Disease: A Cross-Sectional Study in Southern Morocco

2020 ◽  
Vol 7 (3) ◽  
Author(s):  
Abderrahmane Achbani ◽  
Sofiane Ait Wahmane ◽  
Mohamed Elatiqi ◽  
Hasnaa Sine ◽  
Ahmed Kharbach ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Experimental Studies ◽  
Cross Sectional Study ◽  
Age Difference ◽  
Cross Sectional ◽  
Gender And Age ◽  
Initial Symptoms ◽  
Yahr Scale

Background: Parkinson’s disease is the second most frequently reported neurodegenerative disease, behind Alzheimer’s disease. In Morocco, enough information are not available about its prevalence, progression, and characteristics, particularly in Southern regions of the country. Objectives: The current study aimed to investigate gender and age differences in the sociodemographic and clinical profile of Parkinson’s disease patients in southern Morocco. Methods: A cross-sectional descriptive study was conducted on a selected cohort of 180 patients, previously diagnosed with Parkinson’s. Results: The results showed that the onset of the disease was earlier in females compared to males. Besides, we found that the prevalence of rigidity symptoms was slightly higher in younger patients and in patients aged 61 to 70 years old, at the onset of the disease. Importantly, the results showed that the initial symptoms of males were different than females. According to the Hoehn and Yahr scale, the majority (82.6%) of patients of both genders were in the early stage of the disease. Additional statistical analyses, confirmed that the severity of the disease was strongly related to gender (P = 0.02). Conclusions: The findings confirmed that males and females had different clinical motor characteristics in the initial symptoms and progression of Parkinson’s disease. Nevertheless, experimental studies should be conducted to arrive at a real understanding of what underlies these differences.

scholarly journals α-Synuclein pre-formed fibrils induce prion-like protein aggregation and neurotoxicity in C. elegans models of Parkinson's disease

2021 ◽  
Author(s):  
Merry Chen ◽  
Julie Vincent ◽  
Alexis Ezeanii ◽  
Saurabh Wakade ◽  
Shobha Yerigenahally ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Motor Deficit ◽  
Rodent Models ◽  
Neuron Degeneration ◽  
C Elegans ◽  
Dopaminergic Neurodegeneration ◽  
Disease Mechanisms ◽  
The Brain

Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by progressive motor decline and the aggregation of α-synuclein protein. Growing evidence suggests that α-synuclein aggregates may spread from neurons of the digestive tract to the brain in a prion-like manner. While rodent models have recapitulated gut-to-brain α-synuclein transmission, animal models that are amenable to high-throughput investigations are needed to facilitate the discovery of disease mechanisms. Here we describe the first C. elegans models in which feeding with α-synuclein pre-formed fibrils (PFFs) induced prion-like dopamine neuron degeneration and seeding of aggregation of human α-synuclein expressed in the host. PFF acceleration of α-synuclein aggregation in C. elegans muscle cells was associated with a progressive motor deficit, whereas feeding with α-synuclein monomer produced much milder effects. RNAi-mediated knockdown of the C. elegans syndecan sdn-1, and enzymes involved in heparan sulfate proteoglycan biosynthesis, afforded protection from PFF-induced seeding of aggregation and toxicity, as well as dopaminergic neurodegeneration. This work offers new models by which to investigate gut-derived α-synuclein spreading and propagation of disease.

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