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https://www.readbyqxmd.com/read/29032215/determining-mushroom-tyrosinase-inhibition-by-imidazolium-ionic-liquids-a-spectroscopic-and-molecular-docking-study
#1
Mark P Heitz, Jason W Rupp
The inhibition effects of imidazolium ionic liquids (ILs) on the enzyme kinetics of mushroom tyrosinase is reported. A simple UV-VIS spectrophotometric assay was used to measure the reaction kinetics of the reaction between mushroom tyrosinase and L-dopa. Seven different imidazolium ILs, comprised of 1-alkyl-3-methylimidazolium ([Imn1(+)], n=2, 4, 6) cations paired with several anions that included Cl(-), [NO3(-)], methanesulfonate ([MeSO3(-)]), trifluoromethanesulfonate (or triflate, [TFMS(-)]), and bis(trifluoromethylsulfonyl)imide ([Tf2N(-)])...
October 12, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29027462/dual-signal-microbial-biosensor-for-the-detection-of-dopamine-without-inference-from-other-catecholamine-neurotransmitters
#2
Yu-Kuan Lin, Yi-Chun Yeh
Dopamine, one of catecholamine neurotransmitters, plays an important role in many brain functions and behavioral responses. In this study, we developed a novel dual-signal whole-cell biosensor for the detection of dopamine through the generation of red fluorescent proteins and 6-decarboxylated betaxanthin pigments. The proposed system responses specifically to dopamine with a detection limit of 1.43 μM. Furthermore, a combination of dual output signals makes it possible to reduce the interference from other catecholamine neurotransmitters, including L-DOPA, epinephrine, and norepinephrine...
October 13, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29019056/physical-exercise-modulates-l-dopa-regulated-molecular-pathways-in-the-mptp-mouse-model-of-parkinson-s-disease
#3
Cornelius J H M Klemann, Helena Xicoy, Geert Poelmans, Bas R Bloem, Gerard J M Martens, Jasper E Visser
Parkinson's disease (PD) is characterized by the degeneration of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNpc), resulting in motor and non-motor dysfunction. Physical exercise improves these symptoms in PD patients. To explore the molecular mechanisms underlying the beneficial effects of physical exercise, we exposed 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP)-treated mice to a four-week physical exercise regimen, and subsequently explored their motor performance and the transcriptome of multiple PD-linked brain areas...
October 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29018993/dopaminergic-and-non-dopaminergic-gait-components-assessed-by-instrumented-timed-up-and-go-test-in-parkinson-s-disease
#4
Valeria Dibilio, Alessandra Nicoletti, Giovanni Mostile, Simona Toscano, Antonina Luca, Loredana Raciti, Giorgia Sciacca, Rosario Vasta, Calogero Edoardo Cicero, Donatella Contrafatto, Mario Zappia
The timed up and go test (TUG) is a widely used clinical test for the evaluation of balance and mobility. An instrumented version of TUG (iTUG) has been proposed to provide quantitative information on TUG performances. Here, we hypothesized that L-dopa may differently influence gait parameters recorded by a portable inertial sensor. To test this idea, we evaluated iTUG test in patients with Parkinson's disease (PD), both in L-dopa OFF and ON state. Twenty-eight PD patients performed the iTUG. Subjects were instructed to perform the task both in practical "OFF" and "ON" state...
October 10, 2017: Journal of Neural Transmission
https://www.readbyqxmd.com/read/29017909/objectively-measuring-effects-of-electro-acupuncture-in-parkinsonian-rhesus-monkeys
#5
Rui Zhang, Anders H Andersen, Peter A Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M Gash, Richard Grondin, Zhiming Zhang
Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations...
October 7, 2017: Brain Research
https://www.readbyqxmd.com/read/28984404/towards-tuneable-retaining-glycosidase-inhibiting-peptides-by-mimicry-of-a-plant-flavonol-warhead
#6
Ryoji Yoshisada, Lieke van Gijzel, Seino A K Jongkees
Retaining glycosidases are an important class of enzymes involved in glycan degradation. In order to better study the role of specific enzymes in deglycosylation processes, and thereby the importance of particular glycosylation patterns, a set of potent inhibitors each specific to a particular glycosidase would be an invaluable toolkit. Towards this goal, we detail here a more in-depth study of a prototypical macrocyclic peptide inhibitor of the model retaining glycosidase human pancreatic α-amylase (HPA)...
October 6, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28981227/-treatment-of-parkinson-s-disease
#7
S Dethy
Parkinson's disease in a neurodegenerative disorder that affects as many as 1-2 % of persons aged 60 years and older. Parkinson's disease occurs infrequently under 40 years of age, with major genetic implication. Alpha-synuclein plays significant pathogenic role in Parkinson's disease. Therapeutic advances based on a synucleinrelated mechanism are now developed : immunotherapy against alpha-synuclein for example. The diagnosis of Parkinson's disease remains mostly clinical. DatScan® may be helpful to distinguish parkinsonian syndrome and essential tremor...
2017: Revue Médicale de Bruxelles
https://www.readbyqxmd.com/read/28976411/the-efficacy-of-istradefylline-for-treating-mild-wearing-off-in-parkinson-disease
#8
Ichiro Yabe, Mayumi Kitagawa, Ikuko Takahashi, Masaaki Matsushima, Hidenao Sasaki
OBJECTIVES: The adenosine A2A antagonist istradefylline has been used to treat Parkinson disease (PD) with symptoms of wearing-off since 2013 in Japan. Previous randomized controlled trials of istradefylline compared with placebo included PD patients experiencing an average daily OFF time of more than 2 hours. The purpose of this study is to assess the efficacy of 20 mg/d istradefylline in PD subjects experiencing an average daily OFF time of 3 hours or less. METHODS: Fifteen patients were enrolled into this retrospective study...
October 2, 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28963435/carbidopa-is-an-activator-of-aryl-hydrocarbon-receptor-with-potential-for-cancer-therapy
#9
Jiro Ogura, Seiji Miyauchi, Kazumi Shimono, Shengping Yang, Sathisha Gonchigar, Vadivel Ganapathy, Yangzom D Bhutia
Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect...
September 28, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28960663/high-dose-transdermal-nicotine-in-parkinson-s-disease-patients-a-randomized-open-label-blinded-endpoint-evaluation-phase-2-study
#10
Gabriel Villafane, Claire Thiriez, Etienne Audureau, Céline Straczek, Philippe Kerschen, Florence Cormier-Dequaire, Axel Van Der Gucht, Jean-Marc Gurruchaga, Morgane Quéré-Carne, Eva Evangelista, Muriel Paul, Gilles Defer, Philippe Damier, Philippe Remy, Emmanuel Itti, Gilles Fénelon
BACKGROUND: Studies of the effects of nicotine on motor symptoms in Parkinson's disease (PD) brought out discordant results. The aim of the present study was to evaluate the efficacy and safety of high doses of transdermal nicotine on motor symptoms in PD. METHODS: Forty PD patients were randomly assigned to a treated and untreated arm in an open-label study. Treated patients received increasing doses of nicotine to reach 90 mg/day by 11 weeks. This dosage was maintained for 28 weeks (W39), and then reduced over six weeks...
September 28, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28958145/large-aminoacid-transporter-1-selective-liposomes-of-l-dopa-functionalized-amphiphile-for-combating-glioblastoma
#11
Sukanya Bhunia, Venugopal Vangala, Dwaipayan Bhattacharya, Halley Gora Ravuri, Madhusudana Kuncha, Sumana Chakravarty, Ramakrishna Sistla, Arabinda Chaudhuri
Despite significant progresses in neurosurgery and radiation therapy during the past decade, overall survivability (OS) of glioblastoma patients continues to be less than 2 years. Scope of systemic chemotherapy is greatly limited by poor drug transport across blood brain barrier (BBB), and thereby, sub-optimal drug accumulation in glioma tissue. To this end, use of large amino acid transporter-1 (LAT1) over expressed both on brain capillary endothelial cells (BCECs) and glioma cells have begun. Prior reports on the use of LAT1 mediated delivery of model drugs showed their brain accumulations...
September 28, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28956336/regulation-of-striatal-neuron-activity-by-cyclic-nucleotide-signaling-and-phosphodiesterase-inhibition-implications-for-the-treatment-of-parkinson-s-disease
#12
Fernando E Padovan-Neto, Anthony R West
Cyclic nucleotide phosphodiesterase (PDE) enzymes catalyze the hydrolysis and inactivation of cyclic nucleotides (cAMP/cGMP) in the brain. Several classes of PDE enzymes with distinct tissue distributions, cyclic nucleotide selectivity, and regulatory factors are highly expressed in brain regions subserving cognitive and motor processes known to be disrupted in neurodegenerative diseases such as Parkinson's disease (PD). Furthermore, small-molecule inhibitors of several different PDE family members alter cyclic nucleotide levels and favorably enhance motor performance and cognition in animal disease models...
2017: Advances in Neurobiology
https://www.readbyqxmd.com/read/28955204/impairment-of-serotonergic-transmission-by-the-antiparkinsonian-drug-l-dopa-mechanisms-and-clinical-implications
#13
REVIEW
Cristina Miguelez, Abdelhamid Benazzouz, Luisa Ugedo, Philippe De Deurwaerdère
The link between the anti-Parkinsonian drug L-3,4-dihydroxyphenylalanine (L-DOPA) and the serotonergic (5-HT) system has been long established and has received increased attention during the last decade. Most studies have focused on the fact that L-DOPA can be transformed into dopamine (DA) and released from 5-HT terminals, which is especially important for the management of L-DOPA-induced dyskinesia. In patients, treatment using L-DOPA also impacts 5-HT neurotransmission; however, few studies have investigated the mechanisms of this effect...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28952032/neuroprotective-strategies-to-prevent-and-treat-parkinson-s-disease-based-on-its-pathophysiological-mechanism
#14
REVIEW
Yujeong Lee, Min-Sun Kim, Jaewon Lee
Parkinson's disease (PD) is the second most common progressive neurodegenerative disease after Alzheimer's disease. PD exhibits clinical symptoms that include tremors, rigidity, and bradykinesia. Many drugs are available to treat PD, such as, L-dopa, COMT inhibitor, MAO-B inhibitor, and dopamine agonists, but these drugs simply compensate for dopamine loss in PD, and therefore, cannot completely suppress its symptoms or progression. Although the causes of PD are not clearly understood, common pathophysiological pathways, such as, oxidative stress, mitochondrial dysfunction, and neuroinflammation are considered to be etiological factors, and thus, many treatments and interventions have been developed to target these pathophysiological factors...
September 26, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28949038/parkinsonism-without-dopamine-neuron-degeneration-in-aged-l-dopa-responsive-dystonia-knockin-mice
#15
Samuel J Rose, Porter Harrast, Christine Donsante, Xueliang Fan, Valerie Joers, Malú G Tansey, H A Jinnah, Ellen J Hess
BACKGROUND: Recent neuroimaging studies implicate nigrostriatal degeneration as a critical factor in producing late-onset parkinsonism in patients with l-dopa-responsive dystonia-causing mutations. However, postmortem anatomical studies do not reveal neurodegeneration in l-dopa-responsive dystonia patients. These contrasting findings make it unclear how parkinsonism develops in l-dopa-responsive dystonia mutation carriers. METHODS: We prospectively assessed motor dysfunction, responses to dopaminergic challenge, and dopamine neuron degeneration with aging in a validated knockin mouse model bearing a l-dopa-responsive dystonia-causing mutation found in humans...
September 26, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28948862/interaction-between-central-gabaa-receptor-and-dopaminergic-system-on-food-intake-in-neonatal-chicks-role-of-d1-and-gabaa-receptors
#16
Mona Hashemzadeh, Morteza Zendehdel, Vahab Babapour, Negar Panahi
OBJECTIVE: The present study designed to examine the role of central GABAA receptors and dopaminergic system on feeding behavior in neonatal layer-type chicken. METHODS: In this study, 6 experiments designed, each with 4 treatment groups (n = 44 in each experiment). In experiment 1, four groups of FD3 chicks received a dose of either the ICV injection of (A) control solution, (B) L-DOPA (levo-dihydroxyphenylalanine as precursor of dopamine; 125 nmol), (C) Gaboxadol (GABAA receptor agonist, 0...
September 26, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28940893/l-dopa-induced-dyskinesias-motor-fluctuations-and-health-related-quality-of-life-the-copark-survey
#17
Santiago Perez-Lloret, Laurence Negre-Pages, Philippe Damier, Arnaud Delval, Pascal Derkinderen, Alain Destée, Wassilios G Meissner, François Tison, Olivier Rascol
BACKGROUND AND OBJECTIVES: Studies assessing the correlations between L-DOPA-induced dyskinesias (LIDs) and motor fluctuations with Health-related Quality of Life (HRQoL) in Parkinson's Disease (PD) have yielded conflicting results. This study aimed at assessing the relationship between LIDs and motor fluctuations with HRQoL in PD patients, and to assess the relative contribution of their severity and duration in a large sample of PD patients. METHODS: 683 PD patients of the COPARK survey were evaluated...
September 20, 2017: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/28939292/evolution-of-anti-parkinsonian-activity-of-monoterpenoid-1r-2r-6s-3-methyl-6-prop-1-en-2-yl-cyclohex-3-ene-1-2-diol-in-various-in-vivo-models
#18
Elena Valdman, Inga Kapitsa, Еlena Ivanova, Tat Iana Voronina, Oleg Ardashov, Konstantin Volcho, Veniamin Khazanov, Nariman Salakhutdinov
It has been found recently that monoterpenoid (1R,2R,6S)-3-methyl-6-(prop-1-en-2-yl)cyclohex-3-ene-1,2-diol (Diol) demonstrates high antiparkinsonian activity in some animal models. We carried out an extended study of the antiparkinsonian activity of Diol in a set of relevant animal models. Diol (20mg/kg) exhibited an anticataleptogenic effect in the haloperidol-induced catalepsy model and restored motor activity in animals in the reserpine-induced model of oligokinesia. The ability of Diol singly administered before MPTP injection to reduce rigidity comparable to that of activity of L-DOPA (100mg/kg) was found using the model of Parkinsonian syndrome (PS) induced by single injection of MPTP (30mg/kg) to C57BL/6 mice...
September 20, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28931752/l-dopa-sensitizes-vasomotor-tone-by-modulating-the-vascular-alpha1-adrenergic-receptor
#19
Daiki Masukawa, Motokazu Koga, Anna Sezaki, Yuka Nakao, Yuji Kamikubo, Tatsuo Hashimoto, Yuki Okuyama-Oki, Aderemi Caleb Aladeokin, Fumio Nakamura, Utako Yokoyama, Hiromichi Wakui, Hiroshi Ichinose, Takashi Sakurai, Satoshi Umemura, Koichi Tamura, Yoshihiro Ishikawa, Yoshio Goshima
Blood pressure is regulated by extrinsic factors including noradrenaline, the sympathetic neurotransmitter that controls cardiovascular functions through adrenergic receptors. However, the fine-tuning system of noradrenaline signaling is relatively unknown. We here show that l-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of catecholamines, sensitizes the vascular adrenergic receptor alpha1 (ADRA1) through activation of L-DOPA receptor GPR143. In WT mice, intravenous infusion of the ADRA1 agonist phenylephrine induced a transient elevation of blood pressure...
September 21, 2017: JCI Insight
https://www.readbyqxmd.com/read/28921971/paper-sensor-coated-with-a-poly-carboxybetaine-multiple-dopa-conjugate-via-dip-coating-for-biosensing-in-complex-media
#20
Fang Sun, Kan Wu, Hsiang-Chieh Hung, Peng Zhang, Xinran Che, Joshua Smith, Xiaojie Lin, Bowen Li, Priyesh Jain, Qiuming Yu, Shaoyi Jiang
Cellulose paper is an ideal diagnostic platform for low-cost, easily disposable and lightweight implementation, but requires surface modification to achieve detection with high sensitivity and specificity in complex media. In this work, a polymer-catechol conjugate containing a superhydrophilic nonfouling poly(carboxylbetaine) (pCB) and four surface-binding l-3,4-dihydroxyphenylalanine (DOPA) groups, pCB-(DOPA)4, were applied onto a paper-based sensor surface via a simple "graft-to" immersion process to render the surface with both nonfouling and protein functionalizable properties...
October 17, 2017: Analytical Chemistry
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