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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/28635653/virtual-screening-against-phosphoglycerate-kinase-1-in-quest-of-novel-apoptosis-inhibitors
#1
Jie Xia, Bo Feng, Qianhang Shao, Yuhe Yuan, Xiang Simon Wang, Naihong Chen, Song Wu
Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents...
June 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28632695/serum-ceruloplasmin-and-striatal-dopamine-transporter-density-in-parkinson-disease-comparison-with-123i-fp-cit-spect
#2
Yoo Sung Song, Jong-Min Kim, Kyeong Joon Kim, Ji Young Yun, Sang Eun Kim
PURPOSE: In patients with Parkinson disease (PD), decreased serum ceruloplasmin levels have been observed. This study investigated a correlation between serum ceruloplasmin-along with its related serum markers- and striatal presynaptic dopaminergic denervation measured with I-FP-CIT SPECT. METHODS: We analyzed a total of 141 de novo patients divided into 2 groups: the PD group (107 patients with PD) and the disease control group (34 patients with vascular pseudoparkinsonism, essential tremor, or drug-induced parkinsonism)...
June 19, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28628213/changes-in-kynurenine-pathway-metabolism-in-parkinson-patients-with-l-dopa-induced-dyskinesia
#3
Jesper F Havelund, Andreas D Andersen, Michael Binzer, Morten Blaabjerg, Niels H H Heegaard, Egon Stenager, Nils J Faergeman, Jan Bert Gramsbergen
L-DOPA is the most effective drug in the symptomatic treatment of Parkinson's disease, but chronic use is associated with L-DOPA-induced dyskinesia in more than half the patients after 10 years of treatment. L-DOPA treatment may affect tryptophan metabolism via the kynurenine pathway. Altered levels of kynurenine metabolites can affect glutamatergic transmission and may play a role in the development of L-DOPA-induced dyskinesia. In this study we assessed kynurenine metabolites in plasma and cerebrospinal fluid of Parkinson's disease patients and controls...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28625786/drug-induces-depression-like-phenotypes-and-alters-gene-expression-profiles-in-drosophila
#4
Ming-Di Jiang, Ya Zheng, Jia-Lin Wang, Yu-Feng Wang
BACKGROUND: Major depressive disorder (MDD) is a severe mental illness that affects more than 350 million people worldwide. However, the molecular mechanisms of depression are currently unclear. Studies suggest that Drosophila and humans have similar depression-like symptoms under pressure. In this research, we choose Drosophila melanogaster as the animal model to explore the molecular mechanisms that trigger depression. RESULTS: We found that feeding D. melanogaster with the medium containing Levodopa or Chlorpromazine could induce depression-like phenotypes in both behavioral and biochemical biomarkers, including significantly decreased food intake, mating frequency, serotonin (5-HT) concentration, and increased malondialdehyde (MDA) concentration as well as reduced activity of superoxide dismutase (SOD)...
June 15, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28611642/a-case-report-of-severe-delirium-after-amantadine-withdrawal
#5
Franz Marxreiter, Jürgen Winkler, Martin Uhl, Dominik Madžar
Amantadine is frequently used in addition to dopaminergic substances like dopamine agonists or L-Dopa in advanced Parkinson disease (PD). However, adverse effects like hallucinations limit its use. PD patients developing severe psychotic symptoms upon treatment with either dopaminergic substances and/or amantadine need to stop intake of any psychotropic substance. Here, we report the case of a 71-year-old PD patient without previously known cognitive impairment. He presented with drug-induced psychotic symptoms due to changes in his therapeutic regimen (increase in COMT inhibitors, newly introduced MAO B inhibitors)...
January 2017: Case Reports in Neurology
https://www.readbyqxmd.com/read/28607800/effect-of-a-traditional-chinese-herbal-medicine-formulation-on-cell-survival-and-apoptosis-of-mpp-treated-mes-23-5-dopaminergic-cells
#6
Shuifen Ye, Ho Kee Koon, Wen Fan, Yihui Xu, Wei Wei, Chuanshan Xu, Jing Cai
Progressive degeneration of dopaminergic neurons in the substantia nigra (SN) is implicated in Parkinson's disease (PD). The efficacy of these currently used drugs is limited while traditional Chinese medicine (TCM) has been used in the management of neurodegenerative diseases for many years. This study was designed to evaluate the effect of a modified traditional Chinese herbal medicine decoction, Cong Rong Jing (CRJ), on cell survival and apoptosis of 1-methyl-4-phenylpyridinium- (MPP(+)-) treated MES23.5 dopaminergic cells...
2017: Parkinson's Disease
https://www.readbyqxmd.com/read/28606723/changes-in-cortical-excitability-during-paired-associative-stimulation-in-parkinson-s-disease-patients-and-healthy-subjects
#7
Aleksandra Kačar, Sladjan D Milanović, Saša R Filipović, Miloš R Ljubisavljević
Paired associative stimulation (PAS) combines repetitive peripheral nerve stimulation with motor cortex (M1) transcranial magnetic stimulation (TMS), to induce plastic-like changes of cortical excitability. While much attention has been dedicated to post-PAS effects little is known about processes during PAS. We compared the time-course of changes in M1 excitability during standard facilitatory PAS intervention among patients with Parkinson's disease (PD), known to have diminished post-PAS response, and healthy subjects...
June 9, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28604926/ads-5102-amantadine-extended-release-capsules-for-levodopa-induced-dyskinesia-in-parkinson-disease-ease-lid-study-a-randomized-clinical-trial
#8
Rajesh Pahwa, Caroline M Tanner, Robert A Hauser, Stuart H Isaacson, Paul A Nausieda, Daniel D Truong, Pinky Agarwal, Keith L Hull, Kelly E Lyons, Reed Johnson, Mary Jean Stempien
Importance: Medical treatment of levodopa-induced dyskinesia (LID) in Parkinson disease (PD) is an unmet need. Objective: To evaluate the efficacy and safety of ADS-5102 (amantadine) extended-release 274-mg capsules for treatment of LID in patients with PD. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled clinical trial was conducted between May 7, 2014, and July 22, 2015, at 44 North American sites among patients with PD treated with levodopa who experienced at least 1 hour of troublesome dyskinesia per day with at least mild functional impact...
June 12, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28583881/altered-adenosine-2a-and-dopamine-d2-receptor-availability-in-the-6-hydroxydopamine-treated-rats-with-and-without-levodopa-induced-dyskinesia
#9
X Zhou, J Doorduin, P H Elsinga, R A J O Dierckx, E F J de Vries, C Casteels
Several lines of evidence imply alterations in adenosine signaling in Parkinson's disease (PD). Here, we investigated cerebral changes in adenosine 2A receptor (A2AR) availability in 6-hydroxydopamine (6-OHDA)-lesioned rats with and without levodopa-induced dyskinesia (LID) using positron-emission tomography (PET) with [(11)C]preladenant. In parallel dopamine type 2 receptor (D2R) imaging with [(11)C]raclopride PET and behavioral tests for motor and cognitive function were performed. METHODS: Parametric A2AR and D2R binding potential (BPND) images were reconstructed using reference tissue models with midbrain and cerebellum as reference tissue, respectively...
June 2, 2017: NeuroImage
https://www.readbyqxmd.com/read/28578514/the-beneficial-effects-of-hmg-coa-reductase-inhibitors-in-the-processes-of-neurodegeneration
#10
REVIEW
Seyed Soheil Saeedi Saravi, Seyed Sobhan Saeedi Saravi, Alireza Arefidoust, Ahmad Reza Dehpour
Statins, cholesterol lowering drugs, have been demonstrated to exert beneficial effects in other conditions such as primary and progressing neurodegenerative diseases beyond their original role. Observation that statins ameliorate the neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS) and cerebral ischemic stroke, the neuroprotective effects of these drugs are thought to be linked to their anti-inflammatory, anti-oxidative, and anti-excitotoxic properties...
June 3, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28577132/tangeretin-inhibits-neurodegeneration-and-attenuates-inflammatory-responses-and-behavioural-deficits-in-1-methyl-4-phenyl-1-2-3-6-tetrahydropyridine-mptp-induced-parkinson-s-disease-dementia-in-rats
#11
Jin-Song Yang, Xiao-Hong Wu, Hao-Gang Yu, Li-Song Teng
Our aim was to investigate whether tangeretin, a citrus flavonoid, was able to prevent neuroinflammation and improve dementia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced rodent model of Parkinson's disease (PD). MPTP-HCl was infused into the substantia nigra pars compacta of male Sprague-Dawley rats. Tangeretin (50, 100 or 200 mg/kg body weight) was administered orally starting 3 days prior to MPTP injection and was continued for 20 days following injection. MPTP-lesioned rats revealed motor dysfunction in bar test and rota rod tests...
June 2, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28577110/daily-chronomics-of-proteomic-profile-in-aging-and-rotenone-induced-parkinson-s-disease-model-in-male-wistar-rat-and-its-modulation-by-melatonin
#12
Anita Jagota, Ushodaya Mattam
Aging is associated with changes in several basic parameters of circadian timing system (CTS) in mammals leading to circadian dysfunction. We had reported earlier that upon aging and in rotenone induced Parkinson's disease (RIPD) rat model there were significant alterations in the core clock genes expression levels and daily pulses. To identify biomarkers of aging and PD chronomics of proteomic day-night profiles in suprachiasmatic nucleus (SCN), pineal and substantia nigra (SN) in 3 month (m), 12, 24 m and RIPD rat model were studied at two time points i...
June 2, 2017: Biogerontology
https://www.readbyqxmd.com/read/28558910/the-ppii-to-%C3%AE-helix-transition-of-poly-l-lysine-in-methanol-water-solvent-mixtures-accompanied-by-fibrillar-self-aggregation-an-influence-of-fluphenazine-molecules
#13
Katarzyna Cieślik-Boczula
Fourier-transform infrared, vibrational circular dichroism spectroscopy and transmission electron microscopy are used to follow the structural changes of pure and fluphenazine (FPh)-mixed poly-l-lysine (PLL) triggered by variations of the methanol to water ratio in solvent mixtures. FPh molecules are used as an effective psychotic drug but with a strong Parkinson's-related side effect. To answer the question whether FPh molecules can modify the fibril development, the PLL polypeptide was used as a model of α-helix- and PPII-rich fibrils...
August 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28552230/strategies-for-bringing-stem-cell-derived-dopamine-neurons-to-the-clinic-the-kyoto-trial
#14
Jun Takahashi
Concerted efforts are realizing cell-based therapy for Parkinson's disease (PD). In this chapter, I describe efforts at the Center for iPS Cell Research and Application (CiRA), Kyoto University. These efforts use induced pluripotent stem cells (iPSCs) as donor cells. The iPSCs were established as human leukocyte antigen homozygous at CiRA and are intended for allogeneic transplantation. Our manufacturing protocol includes a feeder-free cell culture with laminin fragment LM511-E8 and the sorting of CORIN(+) cells...
2017: Progress in Brain Research
https://www.readbyqxmd.com/read/28539529/membrane-trafficking-illuminates-a-path-to-parkinson-s-disease
#15
Takafumi Hasegawa, Naoto Sugeno, Akio Kikuchi, Toru Baba, Masashi Aoki
Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by progressive movement disability and a variety of non-motor symptoms. The neuropathology of PD consists of the loss of dopaminergic neurons in the midbrain and the appearance of neuronal inclusions called Lewy bodies, which contain insoluble α-synuclein, a relatively small protein originally identified in association with synaptic vesicles in the presynaptic nerve terminals. Drugs that replenish dopamine can partly alleviate the motor symptoms, but they do not cure the disease itself...
2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28535734/investigational-drugs-in-phase-i-and-phase-ii-for-levodopa-induced-dyskinesias
#16
Silvia Cerri, Francesca Siani, Fabio Blandini
Prolonged treatment of Parkinson's disease (PD) with levodopa (L-DOPA) results in motor complications, including motor fluctuations and involuntary movements known as L-DOPA induced dyskinesias (LIDs). LIDs represent an additional cause of disability for PD patients and a major challenge for the clinical neurologist. Preclinical research has provided invaluable insights into the molecular and neural substrates of LIDs, identifying a number of potential targets for new anti-dyskinetic strategies. Areas covered: This review article is centered on drugs currently in Phase I and II clinical trials for LIDs and their relative pharmacological targets, which include glutamate, acetylcholine, serotonin, adrenergic receptors and additional targets of potential therapeutic interest...
June 1, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28528366/cdk5-mediated-phosphorylation-dependent-ubiquitination-and-degradation-of-e3-ubiquitin-ligases-gp78-accelerates-neuronal-death-in-parkinson-s-disease
#17
Qingzhi Wang, Fengjuan Jiao, Pei Zhang, Jianguo Yan, Zheng Zhang, Feng He, Qian Zhang, Zexi Lv, Xiang Peng, Hongwei Cai, Bo Tian
The molecular mechanisms responsible for the loss of dopaminergic neurons in Parkinson's disease (PD) remain obscure. Loss of function of E3 ubiquitin ligases is associated with mitochondria dysfunction, dysfunction of protein degradation, and α-synuclein aggregation, which are major contributors to neurodegeneration in PD. Recent research has thus focused on E3 ubiquitin ligase glycoprotein 78 (GP78); however, the role of GP78 in PD pathogenesis remains unclear. Notably, cyclin-dependent kinase 5 (CDK5) controls multiple cellular events in postmitotic neurons, and CDK5 activity has been implicated in the pathogenesis of PD...
May 20, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515689/current-experimental-studies-of-gene-therapy-in-parkinson-s-disease
#18
REVIEW
Jing-Ya Lin, Cheng-Long Xie, Su-Fang Zhang, Weien Yuan, Zhen-Guo Liu
Parkinson's disease (PD) was characterized by late-onset, progressive dopamine neuron loss and movement disorders. The progresses of PD affected the neural function and integrity. To date, most researches had largely addressed the dopamine replacement therapies, but the appearance of L-dopa-induced dyskinesia hampered the use of the drug. And the mechanism of PD is so complicated that it's hard to solve the problem by just add drugs. Researchers began to focus on the genetic underpinnings of Parkinson's disease, searching for new method that may affect the neurodegeneration processes in it...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28511367/neurobehavioural-changes-in-a-hemiparkinsonian-rat-model-induced-by-rotenone
#19
REVIEW
Sukala Puthuparambil Maniyath, Narayanan Solaiappan, Muthusamy Rathinasamy
INTRODUCTION: Rotenone, a mitochondrial complex I inhibitor is used as a neurotoxin agent to reproduce the neuropathological, and behavioural feature of Parkinson's Disease (PD) in rat. Due to acute and chronic exposure of rotenone with various doses through different routes of administration, mortality is being reported. Low dose takes a longer duration to produce PD symptoms in animals. This present study was designed to create hemiparkinsonian 'partial' lesion model by rotenone at a single moderate dose in two sites of striatum in albino rats and also to assess its toxicity by behavioural parameters and by microscopic study...
March 2017: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28504195/fgf18-protects-against-6-hydroxydopamine-induced-nigrostriatal-damage-in-a-rat-model-of-parkinson-s-disease
#20
Xingzhi Guo, Tingting Liu, Diandian Zhao, Xiaofeng Wang, Dongmei Liu, Yang He, Chang Shan, Yingying Kong, Weiwei Hu, Bei Tao, Lihao Sun, Hongyan Zhao, Shengtian Li, Jianmin Liu
Dopaminergic neuronal injury in the substantia nigra (SN) is a pathological hallmark of Parkinson's disease (PD). However, the underlying mechanism of this injury remains elusive. Since fibroblast growth factor 18 (FGF18) is involved in midbrain development and has been reported to protect neurons from ischemic injury, we investigated whether FGF18 exerted a protective effect on dopaminergic neurons in the SN. In vitro data showed that FGF18 significantly ameliorated the neurotoxicity of 6-hydroxydopamine (6-OHDA) through the AKT/GSK3β signaling pathway...
May 11, 2017: Neuroscience
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