Parkinson’s disease(PD)is a chronic neurological condition that progresses over time.People start to have trouble speaking,writing,walking,or performing other basic skills as dopamine-generating neurons in some brain...Parkinson’s disease(PD)is a chronic neurological condition that progresses over time.People start to have trouble speaking,writing,walking,or performing other basic skills as dopamine-generating neurons in some brain regions are injured or die.The patient’s symptoms become more severe due to the worsening of their signs over time.In this study,we applied state-of-the-art machine learning algorithms to diagnose Parkinson’s disease and identify related risk factors.The research worked on the publicly available dataset on PD,and the dataset consists of a set of significant characteristics of PD.We aim to apply soft computing techniques and provide an effective solution for medical professionals to diagnose PD accurately.This research methodology involves developing a model using a machine learning algorithm.In the model selection,eight different machine learning techniques were adopted:Namely,Random Forest(RF),Decision Tree(DT),Support Vector Machine(SVM),Naïve Bayes(NB),Light Gradient Boosting Machine(LightGBM),K-Nearest Neighbours(KNN),Extreme Gradient Boosting(XGBoost),and Logistic Regression(LR).Subsequently,the concentrated models were validated through 10-fold Cross-Validation and Receiver Operating Characteristic(ROC)—Area Under the Curve(AUC).In addition,GridSearchCV was utilised to measure each algorithm’s best parameter;eventually,the models were trained through the hyperparameter tuning approach.With 98%accuracy,LightGBM had the highest accuracy in this study.RF,KNN,and SVM came in second with 96%accuracy.Furthermore,the performance scores of NB and LR were recorded to be 76%and 83%,respectively.It is to be mentioned that after applying 10-fold cross-validation,the average performance score of LightGBM accounted for 93%.At the same time,the percentage of ROC-AUC appeared at 0.92,which indicates that this LightGBM model reached a satisfactory level.Finally,we extracted meaningful insights and figured out potential gaps on top of PD.By extracting meaningful insights and identifying potential gaps,our study contributes to the significance and impact of PD research.The application of advanced machine learning algorithms holds promise in accurately diagnosing PD and shedding light on crucial aspects of the disease.This research has the potential to enhance the understanding and management of PD,ultimately improving the lives of individuals affected by this condition.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disease in the elderly,accounting for more than 1%of the population aged 65 years.Monogenic inheritance is relatively rare in PD,accounting for approximately 5%to ...Parkinson’s disease(PD)is a common neurodegenerative disease in the elderly,accounting for more than 1%of the population aged 65 years.Monogenic inheritance is relatively rare in PD,accounting for approximately 5%to 10%of PD patients,and there is a growing body of evidence suggesting that multiple genetic risk factors play a significant role in the pathogenesis of PD.Several groups have identified and reported a number of genes carrying mutations associated with affected family members.Mutated genes associated with PD are also candidates for idiopathic PD,and these genes may also carry other mutation sites that increase risk.When multiple genetic risk factors are combined,the risk of PD is increased to a greater extent,and to unravel the pathogenic pathways that lead to different forms of PD.This review focuses on the association of PD genes,such as Parkinson Disease 1-24(PARK1-24),glucosylceramidase(GBA),GTP cyclohydrolase 1(GCH1),fibroblast growth factor 20(FGF20),nuclear receptor-related factor 1(NURR1),NUS1 dehydrodolichyl diphosphate synthase subunit(NUS1),diacylglycerol Lipase Beta(DAGLB),transmembrane protein(TMEM),ubiquinol-cytochrome c reductase core protein 1(UQCRC1),glycoprotein non-metastatic melanoma protein B protein(GPNMB),dynactin 1(DCTN1),LDL receptor related protein 10(LRP10),monoamine oxidase(MAO),ataxin 2(ATXN2),microtubule associated protein tau(MAPT),pantothenate kinase 2(PANK2),spastic parapplegia type 11(SPG11),polymer gamma(POLG),TATA-box binding protein associated factor 1(TAF1),dual specificity tyrosine phosphorylation regulated kinase 1A(Dyrk1a),and crystallin alpha A(CRYAA),with the pathogenesis of PD.We introduce what is currently known about the molecular genetics of PD to help explain the molecular mechanisms leading to the neurodegenerative disease.展开更多
In this study,a systematic review was conducted on the experimental study as well as the clinical application of Tianma(Gastrodia elata Blume),a traditional Chinese medicine,in the prevention and treatment of Parkinso...In this study,a systematic review was conducted on the experimental study as well as the clinical application of Tianma(Gastrodia elata Blume),a traditional Chinese medicine,in the prevention and treatment of Parkinson's disease(PD).On this basis,a summary and outlook were made,so as to provide ideas and theoretical basis for the study,development and utilization of Tianma PD field.展开更多
Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects a...Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects and potential for dependency. This study investigates the effects of a natural supplement combination of Ginkgo Biloba and Acai Extract on cognitive symptoms in a 77-year-old male with PD. The participant underwent a three-month supplementation regimen, with cognitive function assessed using the Montreal Cognitive Assessment (MoCA) test before and after the intervention. The results indicated an improvement in cognitive scores, suggesting that the combination of Ginkgo Biloba and Acai Extract may offer a promising alternative or adjunct to conventional PD treatments. This study highlights the potential of natural supplements in managing PD symptoms and calls for further research with larger sample sizes to confirm these findings. Human data was performed in accordance with the Declaration of Helsinki by the Roxbury District IRB Board (IRB Number: IRB00011767).展开更多
Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighte...Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighteen age-matchednormal controls were studied with ^(99m)Tc-TRODAT-1 SPECT imaging.The regions of interests(ROIs)were drawn manually oncerebellum(CB),occipital cortex(OC)and three transverse plane slice-views of striatums,the semiquantitative BG(back-ground)/[(OC+CB)/2]were then calculated.Results:A lower uptake of ^(99m)Tc-TRODAT-1 in striatums were displayed inthirty-six out of thirty-eight PD patients by visual inspection,compared to controls.In twenty-four PD cases with HYS(Hoehn andYahr scale)stage Ⅰ,a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affectedlimbs than in the same regions of the controls,although the striatal uptake was bilaterally reduced.Using Spearman correlationanalysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions inthe PD group(P<0.05),a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05).However,analysis of variance(ANOVA)did not show any relationship between the decreasing uptake of ^(99m)Tc-TRODAT-1 andincreasing severity of PD patients,although the specific uptake of ^(99m)Tc-TRODAT-1 was continuously decreased in the striatumby visual inspection with the progress of PD from HYS stage Ⅰ to Ⅲ.Conclusion:^(99m)Tc-TRODAT-1 SPECT imaging may serve asa useful method for improving the correct diagnosis of PD.In assessing the role of ^(99m)Tc-TRODAT-1 SPECT in disease severity ofPD,UPDRS can offer a comprehensive index,although the Hoehn and Yahr assessment may be available in part.展开更多
Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characte...Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.展开更多
There are many techniques using sensors and wearable devices for detecting and monitoring patients with Parkinson’s disease(PD).A recent development is the utilization of human interaction with computer keyboards for...There are many techniques using sensors and wearable devices for detecting and monitoring patients with Parkinson’s disease(PD).A recent development is the utilization of human interaction with computer keyboards for analyzing and identifying motor signs in the early stages of the disease.Current designs for classification of time series of computer-key hold durations recorded from healthy control and PD subjects require the time series of length to be considerably long.With an attempt to avoid discomfort to participants in performing long physical tasks for data recording,this paper introduces the use of fuzzy recurrence plots of very short time series as input data for the machine training and classification with long short-term memory(LSTM)neural networks.Being an original approach that is able to both significantly increase the feature dimensions and provides the property of deterministic dynamical systems of very short time series for information processing carried out by an LSTM layer architecture,fuzzy recurrence plots provide promising results and outperform the direct input of the time series for the classification of healthy control and early PD subjects.展开更多
Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of...Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.展开更多
Parkinson’s disease (PD) was frst discovered 200 years ago. The current gold standard of clinical treatment is still mainly levodopa replacement therapy. Traditional Chinese medicine is the fo...Parkinson’s disease (PD) was frst discovered 200 years ago. The current gold standard of clinical treatment is still mainly levodopa replacement therapy. Traditional Chinese medicine is the foundation of traditional medicine in China. Chinese herbs and acu-puncture both exhibit remarkable effcacy in the treatment of PD. Clinical studies on the treatment of PD using Chinese herbs have confrmed that the combined use of Chinese herbs and the levodopa formulation can signifcantly increase the treatment effect and reduce toxic side effects. Basic studies further confrmed that various Chinese herbs and their monomeric substances can protect dopaminergic neurons in PD models. The major mechanisms include anti-infammation, anti-oxidant, anti-apoptosis, neuroprotection, mitochondrial function protection, and regulation of gut microbiota. The function of acupuncture in the treatment of PD has also gradually received extensive attention in China and other countries. Acupuncture not only has peculiar advantages in the improvement of symptoms of PD patients, but also can attenuate adverse drug reactions, delay disease progression, and increase the quality of life of patients. Basic studies further confrmed that acupuncture can improve many motor symptoms in animal models of PD and has cumulative effects and follow-up effects. The major mechanisms include dopamin-ergic neuron protection functions, anti-infammation and anti-oxidant effects, and the regulation of related neuro-transmitters and neural circuits. The clinical application of acupuncture and Chinese herbs still requires strict ran-domized, double-blind, controlled design, multi-centre and large-sample size evidence-based clinical studies and follow-up observations of long-term effcacy to support the effect. In addition, the multi-target and multi-pathway therapeutic mechanisms need further studies.展开更多
In recent years,Parkinson’s Disease(PD)as a progressive syndrome of the nervous system has become highly prevalent worldwide.In this study,a novel hybrid technique established by integrating a Multi-layer Perceptron ...In recent years,Parkinson’s Disease(PD)as a progressive syndrome of the nervous system has become highly prevalent worldwide.In this study,a novel hybrid technique established by integrating a Multi-layer Perceptron Neural Network(MLP)with the Biogeography-based Optimization(BBO)to classify PD based on a series of biomedical voice measurements.BBO is employed to determine the optimal MLP parameters and boost prediction accuracy.The inputs comprised of 22 biomedical voice measurements.The proposed approach detects two PD statuses:0-disease status and 1-good control status.The performance of proposed methods compared with PSO,GA,ACO and ES method.The outcomes affirm that the MLP-BBO model exhibits higher precision and suitability for PD detection.The proposed diagnosis system as a type of speech algorithm detects early Parkinson’s symptoms,and consequently,it served as a promising new robust tool with excellent PD diagnosis performance.展开更多
Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(S...Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(SN)and the formation ofα-synuclein(α-syn)containing inclusion bodies(Lewy pathology)in the surviving neurons.Diagnosis of PD is still based on clinical features.However,owing to the complexity,heterogeneity,and overlapping of its symptoms with other Parkinsonian disorders,correct diagnosis of PD remains a challenge,especially in the early stages.Therefore,there is an urgent need for biomarkers that can help correctly diagnose PD,differentiate PD from other Parkinsonian disorders,monitor the progression of the disease,and evaluate the therapeutic efficacy.Various molecules have been investigated for their utility in diagnosing PD,among whichα-syn is the most extensively investigated one due to its close implication in the etiology and pathogenesis of PD and related diseases.During the past decade,various species ofα-syn,including total,oligomeric,and phosphorylatedα-syn in various tissues,have been investigated for their utility as a potential biomarker for PD diagnosis and differential diagnosis.Various forms ofα-syn in body fluids,including cerebrospinal fluid(CSF),blood plasma,and saliva,are among the ones that are extensively investigated,since the body fluids are relatively accessible compared to the peripheral tissues.The aim of this review is to summarize the progress of studies on the utility ofα-syn in body fluid as a biomarker for PD diagnosis and differential diagnosis.展开更多
Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority amo...Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.展开更多
Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these ...Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.展开更多
Parkinson’s disease(PD)is a common age-related neurodegenerative disease characterized by movement disorders.The hallmark pathological lesions of PD are the formation of Lewy pathology in selected populations of neur...Parkinson’s disease(PD)is a common age-related neurodegenerative disease characterized by movement disorders.The hallmark pathological lesions of PD are the formation of Lewy pathology in selected populations of neurons throughout the nervous system.Braak and his colleagues created a staging system for PD describing the connection between Lewy pathology and disease severity.They proposed that Lewy pathology might be initially triggered by exogenous pathogens targeting the enteric or olfactory nervous system,then spread in a prion-like propagation manner from the peripheral nerves to the lower brainstem and midbrain,before finally reaching higher cortical structures,causing a sequential occurrence of the non-motor and motor symptoms,depending on the lesioned neurons.However,emerging evidence also supports a functional threshold hypothesis proposed by Engelender and Isacson in which Lewy pathology may occur parallelly in the central and peripheral nervous systems and the symptoms only begin when the functional reserve of the affected neurons(and their connecting brain regions)is unable to allow for network compensation.Consequently,early symptoms of PD reflect the loss of function in the least compensated systems,such as the enteric and olfactory nervous systems,rather than the spread of Lewy pathology from the peripheral to the central nervous systems.The current review article provides a comprehensive overview of the evidence supporting a merged mechanism that the neurodegeneration in PD happens to those neurons that are not only intrinsically vulnerable but also affected by the spread of Lewy pathology.展开更多
Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-...Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.展开更多
Deep brain stimulation (DBS) is a non-pharmacological treatment for Parkinson’s disease (PD), and its efficacy depends largely on which anatomical structure (target) is stimulated. The subthalamic nucleus (STN) is on...Deep brain stimulation (DBS) is a non-pharmacological treatment for Parkinson’s disease (PD), and its efficacy depends largely on which anatomical structure (target) is stimulated. The subthalamic nucleus (STN) is one of the most commonly used targets, but stimulation of new targets within the posterior sub-thalamic area (PSA), comprising a group of white matter fibers known as prelemniscal radiations (Raprl), as well as the caudal zonaincerta nucleus (Zic), have proven to be superior at improving certain clinical symptoms. Despite their clinical usefulness, their anatomical connectivity has not been completely described in humans. We performed constrained spherical deconvolution of the signal in diffusion-weighted images and subsequent tractography as a means to non-invasively define the connectivity of the Raprl and Zic in a group of five patients with PD. Further, we used track-density imaging, a novel method to improve the spatial resolution of the acquired images, in order to visualize the small subregions that comprise the PSA with a voxel resolution of 0.2 × 0.2 × 0.2 mm3. Both Raprl and Zic demonstrated high probability of connectivity with the dorsal brainstem, cerebellum, subcortical nuclei (globus pallidum ventral, lateral thalamic nuclei), and cortical areas (orbitofrontal cortex, primary and supplementary motor cortex areas). The connectivity patterns were re-producible between patients and were discretely organized as the tracts entered/exited the PSA, depending on their end points. These findings indicate that the PSA is part of the neuronal circuitry controlling movement, and the precise characterization of its connectivity will aid in our understanding of the net-works involved in PD and how they can be modulated with DBS in order to alleviate symptoms.展开更多
What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-mo...What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major pathological hallmark of all PS consists of a non-physiological detrimental accumulation of protein aggregates which appear intracellularly in neurons and glial cells but also in the extracellular space (Wong and Krainc, 2017). Depending on the pathogenic protein, PS can be divided into synucleinopathies, characterized by aggregation of the protein alpha-Synuclein (aSyn), and tauopathies, characterized by aggregation of the protein Tau (Levin et al., 2016;Poewe et al., 2017). Clinical syndromes of synucleinopathies include Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies, and tauopathies include progressive supranuclear palsy (PSP) and corticobasal degeneration.展开更多
Parkinson's disease(PD) is a common neurodegenerative disorder whose primary pathology features are the degeneration of dopaminergic neurons in the substantia nigra pars compacta(SNc) and the presence of eosinoph...Parkinson's disease(PD) is a common neurodegenerative disorder whose primary pathology features are the degeneration of dopaminergic neurons in the substantia nigra pars compacta(SNc) and the presence of eosinophilic inclusions called Lewy body in the cytoplasm of the remained neurons. Growing evidence suggests that dysfunction of the ubiquitin-proteasome system(UPS) is involved in the etiopathogenesis of PD. In order to investigate the pathogenetic mechanism of ubiquitin-proteasome dysfunction in PD, 2D-differential gel electrophoresis(2D-DIGE) and MALDI-TOF Pro MS were used to determine the proteins, which were differentially expressed, in PC12 cells that had undergone a synthetic proteasomal inhibitor PSI(10 μmol/L) treatment for 24 h. Forty-six protein spots were differentially expressed in response to PSI administration, of which 34 were increased and 12 decreased. Six of these were identified as molecular charperones: endoplasmin precursor(GRP94), heat shock protein 105(HSP105), HSC-70-psl, glucose ruglated protein 75(GRP75), glucose ruglated protein 58(GRP58) and heat shock 27000 protein l(HSP27). The results suggest that the molecular chaperones play an important role in the PD model induced by proteasomal inhibitor.展开更多
基金The funding for thisworkwas provided by theResearch Groups Funding Program,Grant Code(NU/GP/SERC/13/30).
文摘Parkinson’s disease(PD)is a chronic neurological condition that progresses over time.People start to have trouble speaking,writing,walking,or performing other basic skills as dopamine-generating neurons in some brain regions are injured or die.The patient’s symptoms become more severe due to the worsening of their signs over time.In this study,we applied state-of-the-art machine learning algorithms to diagnose Parkinson’s disease and identify related risk factors.The research worked on the publicly available dataset on PD,and the dataset consists of a set of significant characteristics of PD.We aim to apply soft computing techniques and provide an effective solution for medical professionals to diagnose PD accurately.This research methodology involves developing a model using a machine learning algorithm.In the model selection,eight different machine learning techniques were adopted:Namely,Random Forest(RF),Decision Tree(DT),Support Vector Machine(SVM),Naïve Bayes(NB),Light Gradient Boosting Machine(LightGBM),K-Nearest Neighbours(KNN),Extreme Gradient Boosting(XGBoost),and Logistic Regression(LR).Subsequently,the concentrated models were validated through 10-fold Cross-Validation and Receiver Operating Characteristic(ROC)—Area Under the Curve(AUC).In addition,GridSearchCV was utilised to measure each algorithm’s best parameter;eventually,the models were trained through the hyperparameter tuning approach.With 98%accuracy,LightGBM had the highest accuracy in this study.RF,KNN,and SVM came in second with 96%accuracy.Furthermore,the performance scores of NB and LR were recorded to be 76%and 83%,respectively.It is to be mentioned that after applying 10-fold cross-validation,the average performance score of LightGBM accounted for 93%.At the same time,the percentage of ROC-AUC appeared at 0.92,which indicates that this LightGBM model reached a satisfactory level.Finally,we extracted meaningful insights and figured out potential gaps on top of PD.By extracting meaningful insights and identifying potential gaps,our study contributes to the significance and impact of PD research.The application of advanced machine learning algorithms holds promise in accurately diagnosing PD and shedding light on crucial aspects of the disease.This research has the potential to enhance the understanding and management of PD,ultimately improving the lives of individuals affected by this condition.
基金supported partly by Henan University graduate“Talent Program”of Henan Province(SYLYC2023092).
文摘Parkinson’s disease(PD)is a common neurodegenerative disease in the elderly,accounting for more than 1%of the population aged 65 years.Monogenic inheritance is relatively rare in PD,accounting for approximately 5%to 10%of PD patients,and there is a growing body of evidence suggesting that multiple genetic risk factors play a significant role in the pathogenesis of PD.Several groups have identified and reported a number of genes carrying mutations associated with affected family members.Mutated genes associated with PD are also candidates for idiopathic PD,and these genes may also carry other mutation sites that increase risk.When multiple genetic risk factors are combined,the risk of PD is increased to a greater extent,and to unravel the pathogenic pathways that lead to different forms of PD.This review focuses on the association of PD genes,such as Parkinson Disease 1-24(PARK1-24),glucosylceramidase(GBA),GTP cyclohydrolase 1(GCH1),fibroblast growth factor 20(FGF20),nuclear receptor-related factor 1(NURR1),NUS1 dehydrodolichyl diphosphate synthase subunit(NUS1),diacylglycerol Lipase Beta(DAGLB),transmembrane protein(TMEM),ubiquinol-cytochrome c reductase core protein 1(UQCRC1),glycoprotein non-metastatic melanoma protein B protein(GPNMB),dynactin 1(DCTN1),LDL receptor related protein 10(LRP10),monoamine oxidase(MAO),ataxin 2(ATXN2),microtubule associated protein tau(MAPT),pantothenate kinase 2(PANK2),spastic parapplegia type 11(SPG11),polymer gamma(POLG),TATA-box binding protein associated factor 1(TAF1),dual specificity tyrosine phosphorylation regulated kinase 1A(Dyrk1a),and crystallin alpha A(CRYAA),with the pathogenesis of PD.We introduce what is currently known about the molecular genetics of PD to help explain the molecular mechanisms leading to the neurodegenerative disease.
基金National Natural Science Foundation of China(81660671)Science and technology plan project of Science and Technology Department of Yunnan Province(202101AZ070001-172)+1 种基金Key Laboratory of Formulation Granules of Yunnan Province(202105AG070014)National Administration of Traditional Chinese Medicine High-level Key Discipline Construction Project‘Dai Pharmacy’(zyyzdxk-2023192).
文摘In this study,a systematic review was conducted on the experimental study as well as the clinical application of Tianma(Gastrodia elata Blume),a traditional Chinese medicine,in the prevention and treatment of Parkinson's disease(PD).On this basis,a summary and outlook were made,so as to provide ideas and theoretical basis for the study,development and utilization of Tianma PD field.
文摘Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by motor and non-motor symptoms, including cognitive impairment. Current treatments often involve synthetic drugs with significant side effects and potential for dependency. This study investigates the effects of a natural supplement combination of Ginkgo Biloba and Acai Extract on cognitive symptoms in a 77-year-old male with PD. The participant underwent a three-month supplementation regimen, with cognitive function assessed using the Montreal Cognitive Assessment (MoCA) test before and after the intervention. The results indicated an improvement in cognitive scores, suggesting that the combination of Ginkgo Biloba and Acai Extract may offer a promising alternative or adjunct to conventional PD treatments. This study highlights the potential of natural supplements in managing PD symptoms and calls for further research with larger sample sizes to confirm these findings. Human data was performed in accordance with the Declaration of Helsinki by the Roxbury District IRB Board (IRB Number: IRB00011767).
文摘Objective:To investigate the role of ^(99m)Tc-TRODAT-1 SPECT in diagnosis and assessing severity of idiopathicParkinson's disease(PD).Methods:Thirty-eight patients with primary,tentative diagnosis of PD and eighteen age-matchednormal controls were studied with ^(99m)Tc-TRODAT-1 SPECT imaging.The regions of interests(ROIs)were drawn manually oncerebellum(CB),occipital cortex(OC)and three transverse plane slice-views of striatums,the semiquantitative BG(back-ground)/[(OC+CB)/2]were then calculated.Results:A lower uptake of ^(99m)Tc-TRODAT-1 in striatums were displayed inthirty-six out of thirty-eight PD patients by visual inspection,compared to controls.In twenty-four PD cases with HYS(Hoehn andYahr scale)stage Ⅰ,a greater loss of DAT uptake was found in striatum and its subregions contralateral striatum to the affectedlimbs than in the same regions of the controls,although the striatal uptake was bilaterally reduced.Using Spearman correlationanalysis showed that the reduction of the uptake ratios significantly correlated with the UPDRS in striatum and all its subregions inthe PD group(P<0.05),a similar change was also found in the putamen by using the rating scale of Hoehn and Yahr (P<0.05).However,analysis of variance(ANOVA)did not show any relationship between the decreasing uptake of ^(99m)Tc-TRODAT-1 andincreasing severity of PD patients,although the specific uptake of ^(99m)Tc-TRODAT-1 was continuously decreased in the striatumby visual inspection with the progress of PD from HYS stage Ⅰ to Ⅲ.Conclusion:^(99m)Tc-TRODAT-1 SPECT imaging may serve asa useful method for improving the correct diagnosis of PD.In assessing the role of ^(99m)Tc-TRODAT-1 SPECT in disease severity ofPD,UPDRS can offer a comprehensive index,although the Hoehn and Yahr assessment may be available in part.
文摘Parkinson’s disease(PD)is an age-related neurodegenerative ailment that affects dopamine-producing neurons in a specific area of the brain called the substantia nigra of the ventral midbrain.It is clinically characterized by movement disorder and marked with unusual synaptic protein alpha-synuclein accumulation in the brain.To date,only a few Food and Drug Administration(FDA)approved drugs are available on the market for the treatment of PD.Nonetheless,these drugs show parasympathomimetic related adverse events and remarkably higher toxicity;hence,it is important to find more efficacious molecules to treat PD.In our study,We chosen 22 natural compounds as inhibitors that potentially block the alpha-synuclein clump-the pathological hallmark of PD-and provide new avenues for its treatment.Most of these molecules exhibited good pharmacokinetic behaviors,making them decisively favorable drug candidates to cure PD.Molecular docking studies were performed to investigate the binding interactions between natural compounds and alpha-synuclein as anti-Parkinson drug targets.Among the examined compounds,curcumin and piperine emerged as promising phytochemicals with the highest binding affinity,key residual stable bindings and showed a good inhibitory features.Thus,the present study indicates that curcumin and piperine hold the potential to be developed as treatment options against PD.Experimental validations are needed for insights into their mechanism of action and potential clinical application.
文摘There are many techniques using sensors and wearable devices for detecting and monitoring patients with Parkinson’s disease(PD).A recent development is the utilization of human interaction with computer keyboards for analyzing and identifying motor signs in the early stages of the disease.Current designs for classification of time series of computer-key hold durations recorded from healthy control and PD subjects require the time series of length to be considerably long.With an attempt to avoid discomfort to participants in performing long physical tasks for data recording,this paper introduces the use of fuzzy recurrence plots of very short time series as input data for the machine training and classification with long short-term memory(LSTM)neural networks.Being an original approach that is able to both significantly increase the feature dimensions and provides the property of deterministic dynamical systems of very short time series for information processing carried out by an LSTM layer architecture,fuzzy recurrence plots provide promising results and outperform the direct input of the time series for the classification of healthy control and early PD subjects.
基金Project supported by the National Natural Science Foundation of China(Nos.11932003 and 11772019)。
文摘Biophysical computational models are complementary to experiments and theories,providing powerful tools for the study of neurological diseases.The focus of this review is the dynamic modeling and control strategies of Parkinson’s disease(PD).In previous studies,the development of parkinsonian network dynamics modeling has made great progress.Modeling mainly focuses on the cortex-thalamus-basal ganglia(CTBG)circuit and its sub-circuits,which helps to explore the dynamic behavior of the parkinsonian network,such as synchronization.Deep brain stimulation(DBS)is an effective strategy for the treatment of PD.At present,many studies are based on the side effects of the DBS.However,the translation from modeling results to clinical disease mitigation therapy still faces huge challenges.Here,we introduce the progress of DBS improvement.Its specific purpose is to develop novel DBS treatment methods,optimize the treatment effect of DBS for each patient,and focus on the study in closed-loop DBS.Our goal is to review the inspiration and insights gained by combining the system theory with these computational models to analyze neurodynamics and optimize DBS treatment.
基金This work was supported by Beijing Municipal Science & Technology Commission (Z161100002616007), National Key Research and Development Program (2016YFC1306300) and Major Program of National Natural Science Foundation of China (81527901).
文摘Parkinson’s disease (PD) was frst discovered 200 years ago. The current gold standard of clinical treatment is still mainly levodopa replacement therapy. Traditional Chinese medicine is the foundation of traditional medicine in China. Chinese herbs and acu-puncture both exhibit remarkable effcacy in the treatment of PD. Clinical studies on the treatment of PD using Chinese herbs have confrmed that the combined use of Chinese herbs and the levodopa formulation can signifcantly increase the treatment effect and reduce toxic side effects. Basic studies further confrmed that various Chinese herbs and their monomeric substances can protect dopaminergic neurons in PD models. The major mechanisms include anti-infammation, anti-oxidant, anti-apoptosis, neuroprotection, mitochondrial function protection, and regulation of gut microbiota. The function of acupuncture in the treatment of PD has also gradually received extensive attention in China and other countries. Acupuncture not only has peculiar advantages in the improvement of symptoms of PD patients, but also can attenuate adverse drug reactions, delay disease progression, and increase the quality of life of patients. Basic studies further confrmed that acupuncture can improve many motor symptoms in animal models of PD and has cumulative effects and follow-up effects. The major mechanisms include dopamin-ergic neuron protection functions, anti-infammation and anti-oxidant effects, and the regulation of related neuro-transmitters and neural circuits. The clinical application of acupuncture and Chinese herbs still requires strict ran-domized, double-blind, controlled design, multi-centre and large-sample size evidence-based clinical studies and follow-up observations of long-term effcacy to support the effect. In addition, the multi-target and multi-pathway therapeutic mechanisms need further studies.
文摘In recent years,Parkinson’s Disease(PD)as a progressive syndrome of the nervous system has become highly prevalent worldwide.In this study,a novel hybrid technique established by integrating a Multi-layer Perceptron Neural Network(MLP)with the Biogeography-based Optimization(BBO)to classify PD based on a series of biomedical voice measurements.BBO is employed to determine the optimal MLP parameters and boost prediction accuracy.The inputs comprised of 22 biomedical voice measurements.The proposed approach detects two PD statuses:0-disease status and 1-good control status.The performance of proposed methods compared with PSO,GA,ACO and ES method.The outcomes affirm that the MLP-BBO model exhibits higher precision and suitability for PD detection.The proposed diagnosis system as a type of speech algorithm detects early Parkinson’s symptoms,and consequently,it served as a promising new robust tool with excellent PD diagnosis performance.
文摘Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(SN)and the formation ofα-synuclein(α-syn)containing inclusion bodies(Lewy pathology)in the surviving neurons.Diagnosis of PD is still based on clinical features.However,owing to the complexity,heterogeneity,and overlapping of its symptoms with other Parkinsonian disorders,correct diagnosis of PD remains a challenge,especially in the early stages.Therefore,there is an urgent need for biomarkers that can help correctly diagnose PD,differentiate PD from other Parkinsonian disorders,monitor the progression of the disease,and evaluate the therapeutic efficacy.Various molecules have been investigated for their utility in diagnosing PD,among whichα-syn is the most extensively investigated one due to its close implication in the etiology and pathogenesis of PD and related diseases.During the past decade,various species ofα-syn,including total,oligomeric,and phosphorylatedα-syn in various tissues,have been investigated for their utility as a potential biomarker for PD diagnosis and differential diagnosis.Various forms ofα-syn in body fluids,including cerebrospinal fluid(CSF),blood plasma,and saliva,are among the ones that are extensively investigated,since the body fluids are relatively accessible compared to the peripheral tissues.The aim of this review is to summarize the progress of studies on the utility ofα-syn in body fluid as a biomarker for PD diagnosis and differential diagnosis.
基金supported by Hospital Fundacion Nuestra Senora de la Luz,Private Assistance Institution.
文摘Background:Neuroinflammation is an essential event in Parkinson’s disease(PD).Identifying affordable and less invasive biomarkers to make an early diagnosis and monitor therapeutic strategies should be a priority among researchers.The study’s objective was to measure tear levels of cytokines in subjects with PD and their association with motor features and the presence of dry eye symptoms.Methods:A total of 16 subjects with PD and 16 age-and sex-matched controls were included.Movement Disorders Society-Unified Parkinson’s Disease Rating Scale(MDS-UPDRS),Hoehn and Yahr(HY)stage scale,Montreal Cognitive Assessment(MoCA),tear break-up time(TBUT),blink rate(BR),Dry Eye Questionnaire 5(DEQ-5)were examined,and pro-inflammatory cytokines[interleukin(IL)-1β,IL-6,IL-8,IL-10,IL-12p70 and tumor necrosis factor-alpha(TNF-α)]were quantified in tears using the BD Cytometric Bead Array Human Inflammatory Cytokine Kit.Results:Higher tear TNF-αwere quantified in PD compared to controls(2.94±3.95 vs.0.33±0.49 pg/mL,P=0.008).According to DEQ-5,50.0%(n=8)of PD subjects and 12.5%(n=2)controls had dry eye disease(DED).No differences were found in cytokines concentrations between PD patients with DED compared to those without DED.IL-8 was associated with the HY stage,TBUT,DEQ-5,and a better MoCA score.A higher BR correlated moderately with a lower HY stage(r=−0.645,P=0.007),and DED patients have lower BR in PD(12.14±2.54 vs.9.0±2.06 blinks/minute,P=0.031).Conclusions:PD patients have higher levels of TNF-αin tears than age-and sex-matched HC.IL-8 in tears may be both involved in the severity of the disease and in the development of DED in PD.In addition,our findings suggest that as HY stage increases,indicating a more advanced stage,BR decreases,indicating greater motor impairment.Conversely,the presence of DED is associated with higher levels of bradykinesia in PD patients,suggesting a potential relationship between DED and motor impairment severity.
基金the authors are supported by grants from Natural Science Foundation of China(81671244,81371200,and 81401042)a special fund from Key Laboratory of Neurodegenerative Disease,Ministry of Education(PXM2019_026283_000002)+1 种基金Beijing Municipal Science and Technology Commission(Z161100005116011,Z171100000117013)Beijing Municipal commission of Health and Family Planning(PXM2017_026283_000002).
文摘Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.
基金the authors were supported by grants from Natural Science Foundation of China(81671244,81371200,and 81401042)Beijing Municipal Science and Technology Commission(Z161100005116011,Z171100000117013)+1 种基金Beijing Municipal Commission of Health and Family Planning(PXM2017_026283_000002)Beijing Nova Program(Z181100006218052,xx2018096)to Yang WW.
文摘Parkinson’s disease(PD)is a common age-related neurodegenerative disease characterized by movement disorders.The hallmark pathological lesions of PD are the formation of Lewy pathology in selected populations of neurons throughout the nervous system.Braak and his colleagues created a staging system for PD describing the connection between Lewy pathology and disease severity.They proposed that Lewy pathology might be initially triggered by exogenous pathogens targeting the enteric or olfactory nervous system,then spread in a prion-like propagation manner from the peripheral nerves to the lower brainstem and midbrain,before finally reaching higher cortical structures,causing a sequential occurrence of the non-motor and motor symptoms,depending on the lesioned neurons.However,emerging evidence also supports a functional threshold hypothesis proposed by Engelender and Isacson in which Lewy pathology may occur parallelly in the central and peripheral nervous systems and the symptoms only begin when the functional reserve of the affected neurons(and their connecting brain regions)is unable to allow for network compensation.Consequently,early symptoms of PD reflect the loss of function in the least compensated systems,such as the enteric and olfactory nervous systems,rather than the spread of Lewy pathology from the peripheral to the central nervous systems.The current review article provides a comprehensive overview of the evidence supporting a merged mechanism that the neurodegeneration in PD happens to those neurons that are not only intrinsically vulnerable but also affected by the spread of Lewy pathology.
文摘Introduction: Parkinson’s disease (PD) is a progressive neurodegenerative disease more common in those over the age of 60. PD is classically characterized by motor features, although patients may also experience non-motor symptoms. Sleep disturbances, such as rapid eye movement (REM) behavior disorder (RBD), are common in patients with PD and may precede onset of PD. Methods: Data was collected on patients with PD (358 subjects)in a movement disorders clinic at a safety net hospital. In this retrospective database analysis, the association of PD complications with age of onset was evaluated using chi-square tests and logistic regression. Results: Of the PD complications analyzed, there was a significant difference in sleep disturbances by age. Among the 358 PD patients, 120 individuals (33.5%) had information regarding the presence or absence of sleep disturbances. There was a significant difference between the early (onset < 50) and later onset (≥50) groups (p = 0.03) with the odds of having a sleep disorder for the early group 1.6 times that of the late group. Those subjects with siblings who also had PD had 2.0 times the odds of having a sleep disorder compared those without (p = 0.02). Conclusion: Non-motor symptoms such as sleep disorders are a useful predictor of early onset PD. Genetic components of PD impact both motor and non-motor aspects of the disease.
基金supported by the National Council of Science and Technology in Mexico(CONACyT)from grant 0114218-2009a CONACyT scholarship to GGMG(CVU 468870).
文摘Deep brain stimulation (DBS) is a non-pharmacological treatment for Parkinson’s disease (PD), and its efficacy depends largely on which anatomical structure (target) is stimulated. The subthalamic nucleus (STN) is one of the most commonly used targets, but stimulation of new targets within the posterior sub-thalamic area (PSA), comprising a group of white matter fibers known as prelemniscal radiations (Raprl), as well as the caudal zonaincerta nucleus (Zic), have proven to be superior at improving certain clinical symptoms. Despite their clinical usefulness, their anatomical connectivity has not been completely described in humans. We performed constrained spherical deconvolution of the signal in diffusion-weighted images and subsequent tractography as a means to non-invasively define the connectivity of the Raprl and Zic in a group of five patients with PD. Further, we used track-density imaging, a novel method to improve the spatial resolution of the acquired images, in order to visualize the small subregions that comprise the PSA with a voxel resolution of 0.2 × 0.2 × 0.2 mm3. Both Raprl and Zic demonstrated high probability of connectivity with the dorsal brainstem, cerebellum, subcortical nuclei (globus pallidum ventral, lateral thalamic nuclei), and cortical areas (orbitofrontal cortex, primary and supplementary motor cortex areas). The connectivity patterns were re-producible between patients and were discretely organized as the tracts entered/exited the PSA, depending on their end points. These findings indicate that the PSA is part of the neuronal circuitry controlling movement, and the precise characterization of its connectivity will aid in our understanding of the net-works involved in PD and how they can be modulated with DBS in order to alleviate symptoms.
文摘What is the rationale for immunotherapies in Parkinsonian syndromes (PS)? PS are neurodegenerative diseases which are clinically characterized by a hypokinetic phenotype in combination with additional motor and non-motor symptoms. One major pathological hallmark of all PS consists of a non-physiological detrimental accumulation of protein aggregates which appear intracellularly in neurons and glial cells but also in the extracellular space (Wong and Krainc, 2017). Depending on the pathogenic protein, PS can be divided into synucleinopathies, characterized by aggregation of the protein alpha-Synuclein (aSyn), and tauopathies, characterized by aggregation of the protein Tau (Levin et al., 2016;Poewe et al., 2017). Clinical syndromes of synucleinopathies include Parkinson’s disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies, and tauopathies include progressive supranuclear palsy (PSP) and corticobasal degeneration.
文摘Parkinson's disease(PD) is a common neurodegenerative disorder whose primary pathology features are the degeneration of dopaminergic neurons in the substantia nigra pars compacta(SNc) and the presence of eosinophilic inclusions called Lewy body in the cytoplasm of the remained neurons. Growing evidence suggests that dysfunction of the ubiquitin-proteasome system(UPS) is involved in the etiopathogenesis of PD. In order to investigate the pathogenetic mechanism of ubiquitin-proteasome dysfunction in PD, 2D-differential gel electrophoresis(2D-DIGE) and MALDI-TOF Pro MS were used to determine the proteins, which were differentially expressed, in PC12 cells that had undergone a synthetic proteasomal inhibitor PSI(10 μmol/L) treatment for 24 h. Forty-six protein spots were differentially expressed in response to PSI administration, of which 34 were increased and 12 decreased. Six of these were identified as molecular charperones: endoplasmin precursor(GRP94), heat shock protein 105(HSP105), HSC-70-psl, glucose ruglated protein 75(GRP75), glucose ruglated protein 58(GRP58) and heat shock 27000 protein l(HSP27). The results suggest that the molecular chaperones play an important role in the PD model induced by proteasomal inhibitor.