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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/29445781/membrane-bound-comt-isoform-is-an-interfacial-enzyme-general-mechanism-and-new-drug-design-paradigm
#1
Aniket Magarkar, Petteri Parkkila, Tapani Viitala, Tatu Lajunen, Edouard Mobarak, Giuseppe Licari, Oana Cramariuc, Eric Vauthey, Tomasz Róg, Alex Bunker
The enzyme catechol-O-methyltransferase (COMT) has water soluble (S-COMT) and membrane associated (MB-COMT), bitopic, isoforms. Of these MB-COMT is a drug target in relation to the treatment of Parkinson's disease. Using a combination of computational and experimental protocols, we have determined the substrate selection mechanism specific to MB-COMT. We show: (1) substrates with preferred affinity for MB-COMT over S-COMT orient in the membrane in a fashion conducive to catalysis from the membrane surface and (2) binding of COMT to its cofactor ADOMET induces conformational change that drives the catalytic surface of the protein to the membrane surface, where the substrates and Mg 2+ ions, required for catalysis, are found...
February 15, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29434188/dopamine-d2-receptor-mediated-neuroprotection-in-a-g2019s-lrrk2-genetic-model-of-parkinson-s-disease
#2
Alessandro Tozzi, Michela Tantucci, Saverio Marchi, Petra Mazzocchetti, Michele Morari, Paolo Pinton, Andrea Mancini, Paolo Calabresi
Parkinson's disease (PD) is a neurodegenerative disorder in which genetic and environmental factors synergistically lead to loss of midbrain dopamine (DA) neurons. Mutation of leucine-rich repeated kinase2 (Lrrk2) genes is responsible for the majority of inherited familial cases of PD and can also be found in sporadic cases. The pathophysiological role of this kinase has to be fully understood yet. Hyperactivation of Lrrk2 kinase domain might represent a predisposing factor for both enhanced striatal glutamatergic release and mitochondrial vulnerability to environmental factors that are observed in PD...
February 12, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29433810/the-nosology-of-tardive-syndromes
#3
Karen Frei, Daniel D Truong, Stanley Fahn, Joseph Jankovic, Robert A Hauser
Since the original description of side effects of neuroleptics, different terminologies and definitions for tardive dyskinesia (TD) and tardive syndrome (TS) have been used by different authors, and often these two terms have been used interchangeably. This paper proposes a nosology designed to define and clarify various terms and phenomenologies within the TS spectrum. We propose to use the term tardive dyskinesia to refer to the original description of repetitive and complex oral-buccal-lingual (OBL) movements, as well as to the analogous repetitive movements that can appear in the limbs, trunk, or pelvis...
February 6, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/29431985/tremor-sorting-through-the-differential-diagnosis
#4
Paul Crawford, Ethan E Zimmerman
Tremor is an involuntary, rhythmic, oscillatory movement of a body part. It is the most common movement disorder encountered in primary care. The diagnosis of tremor is based on clinical information obtained from the history and physical examination. The most common tremors in patients presenting to primary care physicians are enhanced physiologic tremor, essential tremor, and parkinsonian tremor. All persons have low-amplitude, high-frequency physiologic tremors at rest and during action that are not reported as symptomatic, but can be enhanced by anxiety, medication use, caffeine intake, or fatigue...
February 1, 2018: American Family Physician
https://www.readbyqxmd.com/read/29429051/cilostazol-mediated-nurr1-and-autophagy-enhancement-neuroprotective-activity-in-rat-rotenone-pd-model
#5
Shireen A Hedya, Marwa M Safar, Ashraf K Bahgat
Nuclear receptor related 1 (Nurr1) orphan receptor has emerged as a promising contender in ameliorating Parkinson's disease; thus, finding a suitable activator of Nurr1 receptor is an attracting target for treating PD. Cilostazol, a phosphodiesterase-3 inhibitor, recently showed a favorable neuroprotective activity in multiple devastating central disorders, yet the possible antiparkinsonian activity of the drug has not been fully elucidated. Thus, the aim of this study is to explore the neuroprotective effect of cilostazol in rotenone-induced PD model in rats...
February 10, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29428995/dyskinesias-and-levodopa-therapy-why-wait
#6
REVIEW
Michele Matarazzo, Alexandra Perez-Soriano, A Jon Stoessl
Throughout the years there has been a longstanding discussion on whether levodopa therapy in Parkinson's disease should be started in early vs. later stages, in order to prevent or delay motor complications such as fluctuations and dyskinesias. This controversial topic has been extensively debated for decades, and the prevailing view today is that levodopa should not be postponed. However, there is still fear associated with its use in early stages, especially in younger patients, who are more prone to develop dyskinesias...
February 10, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29416637/liver-x-receptors-agonist-promotes-differentiation-of-rat-bone-marrow-derived-mesenchymal-stem-cells-into-dopaminergic-neuron-like-cells
#7
Oumei Cheng, Xiaoyan Tian, Ying Luo, Shaoshan Mai, Yang Yang, Shengnan Kuang, Qi Chen, Jie Ma, Beibei Chen, Rong Li, Lu Yang, Huan Li, Congli Hu, Jiahua Zhang, Zhihao Chen, Yuke Li, Hui Xia, Ying Xu, Junqing Yang
Dopaminergic (DA) neurons derived from bone marrow derived mesenchymal stem cells (BMSCs) maybe a valuable source for cell replacement therapy in Parkinson disease. Recent studies showed that new functions of LXR and their ligands have been proposed to prevent PD in the adult nervous system. The present study was designed to observe the effect of liver X receptors (LXR) agonist on differentiation of rat BMSCs into DA neurons. Expressions of the neuronal markers (Tuj1 and Nestin), the specific marker of DA neurons (tyrosine hydroxylase, TH), LXR α and LXR β were measured by immunocytochemical assay and TH/Tuj1 positive cells were determined by quantitative cell count analyses...
January 2, 2018: Oncotarget
https://www.readbyqxmd.com/read/29407218/membrane-cholesterol-removal-and-replenishment-affect-rat-and-monkey-brain-monoamine-transporters
#8
Marc Morissette, Nicolas Morin, Claude Rouillard, Thérèse Di Paolo
The dopamine transporter (DAT) is abundantly expressed in the striatum where it removes extracellular dopamine into the cytosol of presynaptic nerve terminals. It is the target of drugs of abuse and antidepressants. There is a loss of the DAT in Parkinson's disease affecting release of levodopa implicated in levodopa-induced dyskinesias. This study investigated the effect of cholesterol on DAT, serotonin transporter (SERT) and vesicular monoamine transporter 2 (VMAT2) in monkey and rat brains in vitro. DAT protein levels measured by Western blot remained unchanged with in vitro methyl-β-cyclodextrin (MCD) incubations to remove membrane cholesterol or with incubations to increase membrane cholesterol content...
January 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29404521/drug-idiosyncrasy-due-to-pirfenidone-presenting-as-acute-liver-failure-case-report-and-mini-review-of-the-literature
#9
REVIEW
Nipun Verma, Pramod Kumar, Suvradeep Mitra, Sunil Taneja, Sahajal Dhooria, Ashim Das, Ajay Duseja, Radha Krishan Dhiman, Yogesh Chawla
Idiosyncratic drug-induced liver injury (DILI) is ranked among the top most common etiologies of acute liver failure (ALF). It carries poor transplant-free survival. Pirfenidone is an anti-inflammatory and antifibrotic drug that is commonly used for the treatment of idiopathic pulmonary fibrosis (IPF). Hepatotoxicity due to pirfenidone is rare and generally manifests as a mild rise in serum aminotransferases. In this mini-review, we report an unusual case of idiosyncratic DILI due to pirfenidone presenting as ALF, with emphasis on the definition, classification, diagnostic criteria, histopathology, molecular markers, and treatment options for DILI and related ALF...
February 2018: Hepatology communications
https://www.readbyqxmd.com/read/29391788/lactoferrin-modified-rotigotine-nanoparticles-for-enhanced-nose-to-brain-delivery-lesa-ms-ms-based-drug-biodistribution-pharmacodynamics-and-neuroprotective-effects
#10
Xiuju Yan, Lixiao Xu, Chenchen Bi, Dongyu Duan, Liuxiang Chu, Xin Yu, Zimei Wu, Aiping Wang, Kaoxiang Sun
Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson's disease (PD). Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs) and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD. Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs) and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry...
2018: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29390878/neuroprotective-effects-of-betulin-in-pharmacological-and-transgenic-caenorhabditis-elegans-models-of-parkinson-s-disease
#11
Chia-Wen Tsai, Rong-Tzong Tsai, Shih-Ping Liu, Chang-Shi Chen, Min-Chen Tsai, Shao-Hsuan Chien, Huey-Shan Hung, Shinn-Zong Lin, Woei-Cherng Shyu, Ru-Huei Fu
Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly. It is characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Current therapeutics for PD provides satisfactory symptom relief but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process...
December 2017: Cell Transplantation
https://www.readbyqxmd.com/read/29377238/pretreatment-of-glial-cell-derived-neurotrophic-factor-and-geranylgeranylacetone-ameliorates-brain-injury-in-parkinson-s-disease-by-its-anti-apoptotic-and-anti-oxidative-property
#12
Peijian Yue, Lin Gao, Xuejing Wang, Xuebing Ding, Junfang Teng
The aim of the present study was to determine the combined effects of glial cell-derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of PD and cellular models of H2 O2 and MPP+ -treated PC12 cells were established. Swimming, pole and traction tests were used to detect behavioral impairment. Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis...
January 27, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29352351/levodopa-induced-dyskinesia-in-parkinson-s-disease-still-no-proof-a-meta-analysis
#13
Alexandros Giannakis, Maria Chondrogiorgi, Christos Tsironis, Athina Tatsioni, Spiridon Konitsiotis
We investigated whether there is a linear relationship between levodopa (LD) dose and treatment duration, and the development of levodopa-induced dyskinesia (LID) among patients with early untreated Parkinson's disease (PD). We performed a meta-analysis of randomized-controlled trials (RCTs) comparing LD monotherapy to any other antiparkinsonian treatment in early PD patients. Meta-regressions were conducted including as covariates the effects of LD dose, treatment duration, and age. We further proceeded in subgroup analyses based on the type of medications in the non-LD monotherapy (control) group and on whether patients in the control group received additional levodopa or not...
January 19, 2018: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29346364/mutations-in-caenorhabditis-elegans-neuroligin-like-glit-1-the-apoptosis-pathway-and-the-calcium-chaperone-crt-1-increase-dopaminergic-neurodegeneration-after-6-ohda-treatment
#14
Sarah-Lena Offenburger, Elisabeth Jongsma, Anton Gartner
The loss of dopaminergic neurons is a hallmark of Parkinson's disease, the aetiology of which is associated with increased levels of oxidative stress. We used C. elegans to screen for genes that protect dopaminergic neurons against oxidative stress and isolated glit-1 (gliotactin (Drosophila neuroligin-like) homologue). Loss of the C. elegans neuroligin-like glit-1 causes increased dopaminergic neurodegeneration after treatment with 6-hydroxydopamine (6-OHDA), an oxidative-stress inducing drug that is specifically taken up into dopaminergic neurons...
January 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29345616/inhibition-of-oxidative-stress-in-cholinergic-projection-neurons-fully-rescues-aging-associated-olfactory-circuit-degeneration-in-drosophila
#15
Ashiq Hussain, Atefeh Pooryasin, Mo Zhang, Laura F Loschek, Marco La Fortezza, Anja B Friedrich, Catherine-Marie Blais, Habibe K Üçpunar, Vicente A Yépez, Martin Lehmann, Nicolas Gompel, Julien Gagneur, Stephan J Sigrist, Ilona C Grunwald Kadow
Loss of the sense of smell is among the first signs of natural aging and neurodegenerative diseases such as Alzheimer's and Parkinson's. Cellular and molecular mechanisms promoting this smell loss are not understood. Here, we show that Drosophila melanogaster also loses olfaction before vision with age. Within the olfactory circuit, cholinergic projection neurons show a reduced odor response accompanied by a defect in axonal integrity and reduction in synaptic marker proteins. Using behavioral functional screening, we pinpoint that expression of the mitochondrial reactive oxygen scavenger SOD2 in cholinergic projection neurons is necessary and sufficient to prevent smell degeneration in aging flies...
January 18, 2018: ELife
https://www.readbyqxmd.com/read/29335539/brain-activity-patterns-in-high-throughput-electrophysiology-screen-predict-both-drug-efficacies-and-side-effects
#16
Peter M Eimon, Mostafa Ghannad-Rezaie, Gianluca De Rienzo, Amin Allalou, Yuelong Wu, Mu Gao, Ambrish Roy, Jeffrey Skolnick, Mehmet Fatih Yanik
Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29327219/pharmacological-insights-into-the-use-of-apomorphine-in-parkinson-s-disease-clinical-relevance
#17
REVIEW
Manon Auffret, Sophie Drapier, Marc Vérin
The present paper consists of a comprehensive review of the literature on apomorphine pharmacological properties and its usefulness in Parkinson's disease (PD). The chemistry, structure-activity relationship, pharmacokinetics and pharmacodynamics of apomorphine are described with regard to its effects on PD symptoms, drug interactions, interindividual variability and adverse events. Apomorphine chemical structure accounts for most of its beneficial and deleterious properties, both dopaminergic and non-dopaminergic...
January 11, 2018: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29324935/right-putamen-and-age-are-the-most-discriminant-features-to-diagnose-parkinson-s-disease-by-using-123i-fp-cit-brain-spet-data-by-using-an-artificial-neural-network-classifier-a-classification-tree-clt
#18
S Cascianelli, C Tranfaglia, M L Fravolini, F Bianconi, M Minestrini, S Nuvoli, N Tambasco, M E Dottorini, B Palumbo
OBJECTIVE: The differential diagnosis of Parkinson's disease (PD) and other conditions, such as essential tremor and drug-induced parkinsonian syndrome or normal aging brain, represents a diagnostic challenge. 123I-FP-CIT brain SPET is able to contribute to the differential diagnosis. Semiquantitative analysis of radiopharmaceutical uptake in basal ganglia (caudate nuclei and putamina) is very useful to support the diagnostic process. An artificial neural network classifier using 123I-FP-CIT brain SPET data, a classification tree (CIT), was applied...
September 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/29324468/switching-antipsychotic-treatment-to-aripiprazole-in-psychotic-patients-with-neuroleptic-induced-tardive-dyskinesia-a-24-week-follow-up-study
#19
Chia-Hsiang Chan, Hung-Yu Chan, Yen-Ching Chen
Aripiprazole is a second-generation antipsychotics, acting as a partial dopamine D2 receptor agonist. Previous studies on aripiprazole for tardive dyskinesia (TD) treatment were limited and inconclusive. This study was aimed to examine the effectiveness of aripiprazole in psychotic patients with a pre-existing TD. This was an open-label 24-week prospective cohort study conducted in a public mental hospital in Northern Taiwan from January 2009 to February 2010.Psychotic patients were cross-titrated of prior antipsychotics with aripiprazole, and the severity of TD was assessed at baseline and at weeks 2, 4, 8, 12, 16, 20, and 24...
January 10, 2018: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/29305532/lrrk2-g2019s-induces-anxiety-depression-like-behavior-prior-to-the-onset-of-motor-dysfunction-with-5-ht1a-receptor-upregulation-in-mice
#20
Juhee Lim, Yeojin Bang, Jong-Hyun Choi, Arum Han, Min-Soo Kwon, Kwang Hyeon Liu, Hyun Jin Choi
Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common genetic cause of Parkinson's disease (PD). The neuropathology of LRRK2 mutation-related PD is indistinguishable from that of idiopathic PD, including increased dopaminergic neurodegeneration and Lewy bodies, but its subtle non-motor phenotypes have not been fully evaluated. In the present study, we examined anxiety/depression-like behaviors and accompanying neurochemical changes in differently aged transgenic (Tg) mice expressing human mutant LRRK2 G2019S...
January 5, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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