scholarly journals The rs13388259 Intergenic Polymorphism in the Genomic Context of theBCYRN1Gene Is Associated with Parkinson’s Disease in the Hungarian Population

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Sándor Márki ◽  
Anikó Göblös ◽  
Eszter Szlávicz ◽  
Nóra Török ◽  
Péter Balicza ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Target Genes ◽  
Neurodegenerative Disorder ◽  
Rare Allele ◽  
Muscle Rigidity ◽  
Genomic Context ◽  
Lncrna Gene ◽  
Low Penetrance Genes

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by bradykinesia, resting tremor, and muscle rigidity. To date, approximately 50 genes have been implicated in PD pathogenesis, including both Mendelian genes with rare mutations and low-penetrance genes with common polymorphisms. Previous studies of low-penetrance genes focused on protein-coding genes, and less attention was given to long noncoding RNAs (lncRNAs). In this study, we aimed to investigate the susceptibility roles of lncRNA gene polymorphisms in the development of PD. Therefore, polymorphisms (n=15) of thePINK1-AS,UCHL1-AS,BCYRN1,SOX2-OT,ANRILandHAR1AlncRNAs genes were genotyped in Hungarian PD patients (n=160) and age- and sex-matched controls (n=167). The rare allele of the rs13388259 intergenic polymorphism, located downstream of theBCYRN1gene, was significantly more frequent among PD patients than control individuals (OR = 2.31;p=0.0015). In silico prediction suggested that this polymorphism is located in a noncoding region close to the binding site of the transcription factor HNF4A, which is a central regulatory hub gene that has been shown to be upregulated in the peripheral blood of PD patients. The rs13388259 polymorphism may interfere with the binding affinity of transcription factor HNF4A, potentially resulting in abnormal expression of target genes, such asBCYRN1.

scholarly journals Potential Role of Caffeine in the Treatment of Parkinson’s Disease

2016 ◽  
Vol 10 (1) ◽  
pp. 42-58 ◽  
Author(s):  
Mohsin H.K. Roshan ◽  
Amos Tambo ◽  
Nikolai P. Pace
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Randomized Clinical Trials ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Muscle Rigidity ◽  
Therapeutic Effects ◽  
Motor Symptoms ◽  
Wide Range

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from bothin vivoandin vitrostudies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2Areceptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

Levodopa Therapy for Parkinson's Disease: History, Current Status and Perspectives

2020 ◽  
Vol 19 (8) ◽  
pp. 572-583
Author(s):  
Helle Bogetofte ◽  
Arezo Alamyar ◽  
Morten Blaabjerg ◽  
Morten Meyer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Side Effects ◽  
Dopaminergic Neurons ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Substantia Nigra Pars Compacta ◽  
Current Status ◽  
Current Evidence ◽  
Muscle Rigidity

Parkinson’s Disease (PD) is a neurodegenerative disorder characterized by a preferential degeneration of dopaminergic neurons in the substantia nigra pars compacta. This results in a profound decrease of striatal dopamine (DA) levels, which in turn leads to the cardinal motor symptoms of PD; muscle rigidity, hypo- and bradykinesia and resting tremor. Even 50 years after its initial use, the DA precursor levodopa (L-dopa), is still the most effective medical therapy for the symptomatic treatment of PD. Long-term L-dopa treatment is however, unfortunately associated with undesirable side effects such as motor fluctuations and dyskinesias. Furthermore, despite the disease alleviating effects of L-dopa, it is still discussed whether L-dopa has a neurotoxic or neuroprotective effect on dopaminergic neurons. Here we review the history of L-dopa, including its discovery, development and current use in the treatment of PD. We furthermore review current evidence of the L-dopa-induced side effects and perspectives of L-dopa treatment in PD compared to other established treatments such as DA-agonists and the inhibitors of catechol-o-methyltransferase and monoamine oxidase B.

scholarly journals ATF4 regulates neuronal death in models of Parkinson’s Disease

2019 ◽  
Author(s):  
Matthew D. Demmings ◽  
Gillian N. Petroff ◽  
Heather E. Tarnowski-Garner ◽  
Sean P. Cregan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Neuronal Death ◽  
Target Genes ◽  
Kinase Inhibitor ◽  
Alpha Synuclein ◽  
Dependent Manner ◽  
Dopaminergic Cell ◽  
Cellular Models

AbstractParkinson’s Disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra resulting in severe motor impairments. However, the mechanisms underlying this neuronal loss remain largely unknown. Activating Transcription Factor 4 (ATF4), a key mediator of the Integrated Stress Response (ISR), is a transcription factor that during prolonged activation can induce the expression of pro-apoptotic target genes. Oxidative stress and ER stress have been implicated in PD and these factors are known to activate the ISR. In this study, we have determined, that both PD neurotoxins (MPP+ and 6-OHDA) and α-synuclein aggregation induced by pre-formed human alpha-synuclein fibrils (PFFs) cause sustained upregulation of ATF4 expression in mouse primary cortical and mesencephalic neurons. Furthermore, we demonstrate that PD neurotoxins induce the expression of the pro-apoptotic factors Chop, Trb3 and Puma in an ATF4-dependent manner. Importantly, using neurons derived from ATF4 +/+ and ATF4 -/- mice, we demonstrate that ATF4 promotes neuronal apoptosis and dopaminergic cell loss in cellular models of PD. Finally, we demonstrate that the eIF2α kinase inhibitor C16 suppresses MPP+ and 6-OHDA induced ATF4 activation and protects against PD neurotoxin induced neuronal death. Taken together these results indicate that ATF4 is a key regulator of dopaminergic cell death induced by PD neurotoxins and pathogenic α-synuclein aggregates and highlight the ISR as a potential therapeutic target in PD.

scholarly journals Behavioral Tests in Neurotoxin-Induced Animal Models of Parkinson’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 1007
Author(s):  
E. Maruthi Prasad ◽  
Shih-Ya Hung
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Neurodegenerative Disorder ◽  
Mitochondrial Respiratory Chain ◽  
Current Treatment ◽  
Muscle Rigidity ◽  
Motor Symptoms ◽  
Dopamine Depletion ◽  
Pathologic Features

Currently, neurodegenerative diseases are a major cause of disability around the world. Parkinson’s disease (PD) is the second-leading cause of neurodegenerative disorder after Alzheimer’s disease. In PD, continuous loss of dopaminergic neurons in the substantia nigra causes dopamine depletion in the striatum, promotes the primary motor symptoms of resting tremor, bradykinesia, muscle rigidity, and postural instability. The risk factors of PD comprise environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular injury, aging, and hereditary defects. The pathologic features of PD include impaired protein homeostasis, mitochondrial dysfunction, nitric oxide, and neuroinflammation, but the interaction of these factors contributing to PD is not fully understood. In neurotoxin-induced PD models, neurotoxins, for instance, 6-hydroxydopamine (6-OHDA), 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-Methyl-4-phenylpyridinium (MPP+), paraquat, rotenone, and permethrin mainly impair the mitochondrial respiratory chain, activate microglia, and generate reactive oxygen species to induce autooxidation and dopaminergic neuronal apoptosis. Since no current treatment can cure PD, using a suitable PD animal model to evaluate PD motor symptoms’ treatment efficacy and identify therapeutic targets and drugs are still needed. Hence, the present review focuses on the latest scientific developments in different neurotoxin-induced PD animal models with their mechanisms of pathogenesis and evaluation methods of PD motor symptoms.

scholarly journals Spinal Anesthesia for Laparoscopic Cholecystectomy in Parkinson’s disease

2018 ◽  
Vol 56 (211) ◽  
pp. 701-704
Author(s):  
Binod Gautam ◽  
Bikash Baral
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Laparoscopic Cholecystectomy ◽  
General Anaesthesia ◽  
Spinal Anaesthesia ◽  
Neurodegenerative Disorder ◽  
Abdominal Pressure ◽  
Muscle Rigidity ◽  
Sensory Blockade ◽  
Organ Systems

Parkinson’s disease, a neurodegenerative disorder, presents with resting tremor, muscle rigidity and bradykinesia. Affecting multiple organ-systems, it’s an important cause of peri-operative morbidity. General anaesthesia may deteriorate cardio-pulmonary and neuro-cognitive functions; moreover, medications used may interact with anti-parkinsonian agents. Spinal anaesthesia is usually avoided in Parkinson’s disease. However, it offers neurologic monitoring and less surgical stress response and avoids complications of general anaesthesia. This case report aims to demonstrate application of spinal anaesthesia for laparoscopic cholecystectomy in a Parkinson’s elderly with pulmonary dysfunction and anticipated difficult airway management. Sensory blockade of third thoracic dermatome was achieved. Bupivacaine was instilled intra-peritoneally. Surgery was smooth at low intra-abdominal pressure. Regular Paracetamol provided satisfactory post-operative analgesia. Single episode of post-operative vomiting was effectively managed. Without deterioration, patient was discharged from hospital on third day. Spinal anaesthesia is a valid technique for laparoscopic cholecystectomy in needy patients with multiple peri-operative risks.

scholarly journals Analysis and Exposure of Parkinson’s Disease Signal in the Vicinity of Wavelet Transform

2011 ◽  
pp. 26-31
Author(s):  
P.V.Rama Raju ◽  
P.N.T.L. Durga ◽  
B.G.S. Anusha ◽  
A. Bhogeswararao ◽  
M.BalaSai Krishna ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Decision Making ◽  
Parkinson's Disease ◽  
Wavelet Transform ◽  
Neurodegenerative Disorder ◽  
Body Movement ◽  
Muscle Rigidity ◽  
Sequential Order ◽  
Accurate Picture ◽  
Scientific Decision

Parkinson's disease (PD) is a gradual progressive central neurodegenerative disorder that affects body movement and is characterized by symptoms such as muscle rigidity, resting tremors, loss of facial expression, hypophonia, diminished blinking, and akinesia [4]. This work aims at providing new insights on the Parkinson's disease fragmentation problem using wavelets [1, 2, 3]. The present work describes a computer model to provide a more accurate picture of the Parkinson's disease (PD) signal processing via Wavelet Transform [7, 8, 9, 10]. The Matlab techniques have been uses which provide a system oriented scientific decision making modal [7, 8]. Within this practice the applied signal has been compared in a sequential order with dissimilar cases in attendance in the database. Special biomedical signals have been considered from Gait in Aging and Disease Database [6] and Physio bank [5]. Analyze the signal under consideration and renowned the holder 100% truthfully.

scholarly journals Parkinson's Disease – An Unusual Case of Prolonged Invasive Home Ventilation

JMS SKIMS ◽  
2013 ◽  
Vol 16 (2) ◽  
pp. 97-98
Author(s):  
Abdul Qayoom Dar ◽  
Murtaza Asif Ali
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Unusual Case ◽  
Neurodegenerative Disorder ◽  
Motor Dysfunction ◽  
Muscle Rigidity ◽  
Patient Needs ◽  
Home Ventilation ◽  
Impaired Ability ◽  
The Impact

Parkinson's disease is a neurodegenerative disorder characterized by muscle rigidity, tremor, slowing or loss of physical movement. The impact of the disease is indicated by the fact that mortality is two to five times as high among affected persons as among age matched controls resulting in reduction in life expectancy. Amongst the motor dysfunction, swallowing disturbances can lead to drooling and impaired ability to swallow. These could cause aspiration pneumonia and death. We report a case of prolonged invasive home ventilation. Patient needs four hours of ventilation a day and uses Passy Muir Valve PMV 2000 for speech. JMS 2013;16(2):97-98

Effects of Osteopathic Manipulative Treatment on Pulmonary Function in a Parkinson’s Disease Patient

2020 ◽  
Vol 30 (4) ◽  
pp. 26-30
Author(s):  
Sheldon C. Yao
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Pulmonary Function ◽  
Respiratory Symptoms ◽  
Neurodegenerative Disorder ◽  
Disease Patient ◽  
Muscle Rigidity ◽  
Osteopathic Manipulative Treatment ◽  
Highly Correlated ◽  
Positive Effect

Abstract Parkinson’s disease (PD) is a neurodegenerative disorder with motor symptoms including resting tremor, bradykinesia, cogwheel rigidity, and postural instability. Parkinson’s patients can also exhibit respiratory symptoms. The muscle rigidity associated with PD has been found to be highly correlated with the severity of pulmonary dysfunction. This case details the treatment of a 73-year-old PD patient who presented with acute dyspnea that resolved with application of osteopathic manipulative treatment (OMT). Treatment focused on addressing thoracic cage musculoskeletal restrictions, balancing autonomic flow, and improving circulatory and lymphatic flow. The patient’s respiratory symptoms were alleviated despite a lack of significant pulmonary function test changes immediately post-treatment. This case demonstrates the positive effect of integrating OMT for the treatment of pulmonary symptoms in PD.

scholarly journals Calmodulin and Its Binding Proteins in Parkinson’s Disease

2021 ◽  
Vol 22 (6) ◽  
pp. 3016
Author(s):  
Anastasiia Bohush ◽  
Wiesława Leśniak ◽  
Serge Weis ◽  
Anna Filipek
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dopaminergic Neurons ◽  
Binding Proteins ◽  
Neurodegenerative Disorder ◽  
Lewy Bodies ◽  
Synaptic Proteins ◽  
Muscle Rigidity ◽  
Cellular Processes ◽  
Intracellular Signals

Parkinson’s disease (PD) is a neurodegenerative disorder that manifests with rest tremor, muscle rigidity and movement disturbances. At the microscopic level it is characterized by formation of specific intraneuronal inclusions, called Lewy bodies (LBs), and by a progressive loss of dopaminergic neurons in the striatum and substantia nigra. All living cells, among them neurons, rely on Ca2+ as a universal carrier of extracellular and intracellular signals that can initiate and control various cellular processes. Disturbances in Ca2+ homeostasis and dysfunction of Ca2+ signaling pathways may have serious consequences on cells and even result in cell death. Dopaminergic neurons are particularly sensitive to any changes in intracellular Ca2+ level. The best known and studied Ca2+ sensor in eukaryotic cells is calmodulin. Calmodulin binds Ca2+ with high affinity and regulates the activity of a plethora of proteins. In the brain, calmodulin and its binding proteins play a crucial role in regulation of the activity of synaptic proteins and in the maintenance of neuronal plasticity. Thus, any changes in activity of these proteins might be linked to the development and progression of neurodegenerative disorders including PD. This review aims to summarize published results regarding the role of calmodulin and its binding proteins in pathology and pathogenesis of PD.

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.

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