Current Therapeutic Strategies and Perspectives for Neuroprotection in Parkinson’s Disease

2020 ◽  
Vol 26 (37) ◽  
pp. 4738-4746
Author(s):  
Mohan K. Ghanta ◽  
P. Elango ◽  
Bhaskar L. V. K. S.
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Therapeutic Strategies ◽  
Neuroprotective Agents ◽  
Striatal Neurons ◽  
The Status ◽  
Advanced Stages ◽  
Dopaminergic Pathways

Parkinson’s disease is a progressive neurodegenerative disorder of dopaminergic striatal neurons in basal ganglia. Treatment of Parkinson’s disease (PD) through dopamine replacement strategies may provide improvement in early stages and this treatment response is related to dopaminergic neuronal mass which decreases in advanced stages. This treatment failure was revealed by many studies and levodopa treatment became ineffective or toxic in chronic stages of PD. Early diagnosis and neuroprotective agents may be a suitable approach for the treatment of PD. The essentials required for early diagnosis are biomarkers. Characterising the striatal neurons, understanding the status of dopaminergic pathways in different PD stages may reveal the effects of the drugs used in the treatment. This review updates on characterisation of striatal neurons, electrophysiology of dopaminergic pathways in PD, biomarkers of PD, approaches for success of neuroprotective agents in clinical trials. The literature was collected from the articles in database of PubMed, MedLine and other available literature resources.

scholarly journals A Simple and Effective Approach Based on a Multi-Level Feature Selection for Automated Parkinson’s Disease Detection

2022 ◽  
Vol 12 (1) ◽  
pp. 55
Author(s):  
Fatih Demir ◽  
Kamran Siddique ◽  
Mohammed Alswaitti ◽  
Kursat Demir ◽  
Abdulkadir Sengur
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Feature Selection ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Bayesian Optimization ◽  
L1 Norm ◽  
Bayesian Optimization Algorithm ◽  
Knn Classifier ◽  
Multi Level

Parkinson’s disease (PD), which is a slowly progressing neurodegenerative disorder, negatively affects people’s daily lives. Early diagnosis is of great importance to minimize the effects of PD. One of the most important symptoms in the early diagnosis of PD disease is the monotony and distortion of speech. Artificial intelligence-based approaches can help specialists and physicians to automatically detect these disorders. In this study, a new and powerful approach based on multi-level feature selection was proposed to detect PD from features containing voice recordings of already-diagnosed cases. At the first level, feature selection was performed with the Chi-square and L1-Norm SVM algorithms (CLS). Then, the features that were extracted from these algorithms were combined to increase the representation power of the samples. At the last level, those samples that were highly distinctive from the combined feature set were selected with feature importance weights using the ReliefF algorithm. In the classification stage, popular classifiers such as KNN, SVM, and DT were used for machine learning, and the best performance was achieved with the KNN classifier. Moreover, the hyperparameters of the KNN classifier were selected with the Bayesian optimization algorithm, and the performance of the proposed approach was further improved. The proposed approach was evaluated using a 10-fold cross-validation technique on a dataset containing PD and normal classes, and a classification accuracy of 95.4% was achieved.

scholarly journals Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Verónica Muñoz-Soriano ◽  
Nuria Paricio
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Model Organism ◽  
Disease Process ◽  
Therapeutic Strategies ◽  
Progressive Loss ◽  
Novel Therapeutic Strategies ◽  
Drosophila Models

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies.

scholarly journals The Cataleptic, Asymmetric, Analgesic, and Brain Biochemical Effects of Parkinson’s Disease Can Be Affected by Toxoplasma gondii Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Mahnaz Taherianfard ◽  
Moslem Riyahi ◽  
Mostafa Razavi ◽  
Zahedeh Bavandi ◽  
Narges Eskandari Roozbahani ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Toxoplasma Gondii ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Latency Time ◽  
Striatal Neurons ◽  
Nociceptive Behavior ◽  
Pd Control ◽  
Nissl Body

Purpose. Parkinson’s disease (PD) is a neurodegenerative disorder with progressive motor defects. Therefore, the aim of the present investigation was to examine whether catalepsy, asymmetry, and nociceptive behaviors; the Nissl-body and neuron distribution; brain-derived neurotrophic factor (BDNF); malondialdehyde (MDA); total antioxidant capacity (TAC) levels; and the percentage of dopamine depletion of striatal neurons in the rat model of Parkinson’s disease (PD) can be affected by Toxoplasma gondii (TG) infection. Methods. Fifty rats were divided into five groups: control (intact rats), sham (rats which received an intrastriatal injection of artificial cerebrospinal fluid (ACSF)), PD control (induction of PD without TG infection), TG control (rats infected by TG without PD induction), and PD infected (third week after PD induction, infection by TG was done). PD was induced by the unilateral intrastriatal microinjection of 6-hydroxydopamine (6-OHDA) and ELISA quantified dopamine, BDNF, MDA, and TAC in the striatum tissue. Cataleptic, asymmetrical, nociceptive, and histological alterations were determined by bar test, elevated body swing test, formalin test, and Nissl-body and neuron counting in the striatal neurons. Results. The results demonstrated that PD could significantly increase the number of biased swings, descent latency time, and nociceptive behavior and decrease the distribution of Nissl-stained neurons compared to the control and sham groups. TG infection significantly improved biased swing, descent latency time, nociceptive behavior, and the Nissl-body distribution in striatal neurons in comparison to the PD control group. The striatal level of BDNF in the PD-infected and TG control groups significantly increased relative to the PD control group. The striatal MDA was significantly higher in the PD control than other groups, while striatal TAC was significantly lower in the PD control than other groups. Conclusions. The current study indicates that TG infection could improve the cataleptic, asymmetric, nociceptive and behaviors; the level of striatal dopamine release; BDNF levels; TAC; and MDA in PD rats.

scholarly journals KARAKTERISTIK KLINIS DAN DERAJAT BERAT GEJALA MOTORIK PENYAKIT PARKINSON DI RSUP SANGLAH DAN RSUD WANGAYA DENPASAR

2020 ◽  
Vol 3 (1) ◽  
pp. 6-11
Author(s):  
Pristanova Larasanti ◽  
Dewa Putu Gede Purwa Samatra ◽  
Sri Yenni Trisnawati ◽  
I Ketut Sumada
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
General Hospital ◽  
Neurodegenerative Disorder ◽  
Cross Sectional ◽  
Disability Adjusted Life ◽  
Life Years ◽  
The Status ◽  
Cross Sectional Design ◽  
Global Burden Disease

Background: Parkinson's Disease (PD) is the second most common neurodegenerative disorder. The Global Burden Disease (GBD) report published in 2018 estimated there were 6.1 million individuals suffering from PD globally and causing 3.2 million Disability-Adjusted Life Years (DALY) and 211,296 deaths in 2016. Disability mainly caused by motor symptoms. This study aims to determine the clinical characteristics and motor severity in PD patients in Sanglah and Wangaya General Hospital Denpasar. Method: Descriptive observational study with cross-sectional design. Samples taken consecutively from all patients diagnosed with PD at Neurology Polyclinic in Sanglah and Wangaya General Hospital from December 2018 - February 2019. Result: From 47 subjects with PD, 72.3% were male, 83% had onset within 1-5 years, and the mean age was 63.87 ± 8.67 years. As many as 44.7% subjects had Hoehn-Yahr 2 stadium, with an average MDS-UPDRS III score of 35.11 ± 21.39, and 48.9% subjects had mild severity. As many as 59.6% subjects had the status of ON. Motor severity showed a trend that increases with increasing staging, but was not seen when compared to the onset. This result might be affected by the ON/OFF status during examination. Conclusion: Parkinson's disease in Sanglah and Wangaya General Hospital is more common in men and over the age of 50 years, and most are found in moderate severity. There is a trend of worsening motor severity with the increasing Hoehn-Yahr stadium. Examination using UPDRS-III is recommended to be done both on ON and OFF state to get more sensitive results

Multiclass recognition of Alzheimer’s and Parkinson’s disease using various machine learning techniques: A study

2021 ◽  
Author(s):  
Chetan Balaji ◽  
D. S. Suresh
Keyword(s):  
Machine Learning ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Neurodegenerative Disorder ◽  
Early Stage ◽  
Ensemble Methods ◽  
Machine Learning Techniques ◽  
Support Vector ◽  
Input Space

The aging population is primarily affected by Alzheimer’s disease (AD) that is an incurable neurodegenerative disorder. There is a need for an automated efficient technique to diagnose Alzheimer’s in its early stage. Various techniques are used to diagnose AD. EEG and neuroimaging methodologies are widely used to highlight changes in the electrical activity of the brain signals that are helpful for early diagnosis. Parkinson’s disease (PD) is a major neurological disease that results in an average of 50,000 new clinical diagnoses worldwide every year. The voice features are majorly used as the main means to diagnose PD. The major symptoms of PD are loss of intensity, the monotony of loudness and pitch, reduction in stress, unidentified silences, and dysphonia. Even though various innovative models are proposed by explorers about Alzheimer’s and Parkinson’s classification diseases, still there is a need for efficient learning methodologies and techniques. This paper provides a review on using machine learning (ML) together with several feature extraction techniques that is helpful in the early detection of AD with Parkinson’s. The novelty and objective of this study are that the CAD technique is used to improve the accuracy of early diagnosis of AD. The proposed technique depends on the nonlinear process for data dimension reduction, feature removal, and classification using kernel-based support vector machine (SVM) classifiers. The dimension of the input space is radically diminished with kernel methods. As the learning set is labeled, it creates sense to utilize this information to make a dependable method of dropping the input space dimension. The different techniques of ML are explained under the major approaches viz. SVM, artificial neural network (ANN), deep learning (DL), and ensemble methods. A comprehensive assessment is presented at SVM, ANN, and DL approaches for better detection of Alzheimer’s with PD highlighting future insights.

scholarly journals FLIM Analysis of Intracellular Markers Associated With the Development of Parkinson's Disease in Cellular Model

2018 ◽  
pp. S673-S683 ◽  
Author(s):  
M. POKUSA ◽  
A. KRÁĽOVÁ TRANČÍKOVÁ
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Microscopic Analysis ◽  
Cellular Level ◽  
Disease Stage ◽  
Cytoplasmic Inclusions ◽  
Advanced Stages ◽  
Intracellular Changes

Parkinson's disease (PD) is currently the second most common neurodegenerative disorder in the world. Major features of cell pathology of the disease include the presence of cytoplasmic inclusions called Lewy bodies, which are composed of aggregated proteins. The presence of Lewy's body is associated with more advanced stages of the disease when considering irreversible changes. Precise identification of the disease stage at a cellular level presents the critical tool in developing early diagnostics and/or prevention of PD. The aim of our work is to introduce sensitive microscopic analysis in living cells, focused on initial intracellular changes and thus capable to detect earlier stages of the disease.

Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Paper Spray ◽  
Molecular Features ◽  
Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

Visual Effects of Deep Brain Stimulation in a Patient with Parkinson’s Disease

2019 ◽  
pp. 158-173
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Visual System ◽  
Brain Stimulation ◽  
Neurodegenerative Disorder ◽  
Initial Examination ◽  
Before And After ◽  
Deep Brain ◽  
Cover Test

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by a dopamine deficiency that presents with motor symptoms. Visual disorders can occur concomitantly but are frequently overlooked. Deep brain stimulation (DBS) has been an effective treatment to improve tremors, stiffness and overall mobility, but little is known about its effects on the visual system. Case Report: A 75-year-old Caucasian male with PD presented with longstanding binocular diplopia. On baseline examination, the best-corrected visual acuity was 20/25 in each eye. On observation, he had noticeable tremors with an unsteady gait. Distance alternating cover test showed exophoria with a right hyperphoria. Near alternating cover test revealed a significantly larger exophoria accompanied by a reduced near point of convergence. Additional testing with a 24-2 Humphrey visual field and optical coherence tomography (OCT) of the nerve and macula were unremarkable. The patient underwent DBS implantation five weeks after initial examination, and the device was activated four weeks thereafter. At follow up, the patient still complained of intermittent diplopia. There was no significant change in the manifest refraction or prism correction. On observation, the patient had remarkably improved tremors with a steady gait. All parameters measured were unchanged. The patient was evaluated again seven months after device activation. Although vergence ranges at all distances were improved, the patient was still symptomatic for intermittent diplopia. OCT scans of the optic nerve showed borderline but symmetric thinning in each eye. All other parameters measured were unchanged. Conclusion: The case found no significant changes on ophthalmic examination after DBS implantation and activation in a patient with PD. To the best of the authors’ knowledge, there are no other cases in the literature that investigated the effects of DBS on the visual system pathway in a patient with PD before and after DBS implantation and activation.

Peripheral Immunity, Immunoaging and Neuroinflammation in Parkinson’s Disease

2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Immune System ◽  
Neurodegenerative Disorder ◽  
Neurodegenerative Process ◽  
Progressive Degeneration ◽  
Cytokine Levels ◽  
Inflammatory Phenotype ◽  
Immune Challenges

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.

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