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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/28109635/impact-of-high-cholesterol-in-a-parkinson-s-disease-model-prevention-of-lysosomal-leakage-versus-stimulation-of-%C3%AE-synuclein-aggregation
#1
Ida Eriksson, Sangeeta Nath, Per Bornefall, Ana Maria Villamil Giraldo, Karin Öllinger
Parkinson's disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated α-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), we found that MPP(+)-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells...
January 16, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28106982/a-novel-iron-ii-preferring-dopamine-agonist-chelator-as-potential-symptomatic-and-neuroprotective-therapeutic-agent-for-parkinson-s-disease
#2
Banibrata Das, Ashoka Kandegedara, Liping Xu, Tamara Antonio, Timothy L Stemmler, Maarten E A Reith, Aloke K Dutta
Parkinson's disease (PD) is a progressive neurodegenerative disorder and development of disease-modifying treatment is still an unmet medical need. Considering the implication of free iron (II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-)-12 (D-607) as a multitarget-directed ligand against PD. Binding and functional assays at dopamine D2/D3 receptors indicate potent agonist activity of (-)-12. The molecule displayed an efficient preferential iron (II) chelation properties along with potent in vivo activity in a reserpinized PD animal model...
January 20, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28100851/effects-of-propofol-on-oxidative-stress-parameters-in-selected-parts-of-the-brain-in-a-rat-model-of-parkinson-disease
#3
Ewa Romuk, Wioletta Szczurek, Przemysław Nowak, Marta Skowron, Bernard Prudel, Edyta Hudziec, Ewa Chwalińska, Ewa Birkner
INTRODUCTION: Propofol is an intravenous sedative-hypnotic agent that is commonly used to induce and maintain general anaesthesia. This drug has antioxidant properties, which are partly caused by a phenolic structure similar to α-tocopherol. The present study aimed to evaluate the effect of propofol on the level of oxidative stress biomarkers in the frontal cortex, striatum, thalamus, hippocampus and cerebellum in rats with experimental Parkinson's disease (PD). MATERIAL/METHODS: The experiment was performed on 24 male Wistar rats assigned to the following groups: 1 - control; 2 - PD; 3 - PD with propofol...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28096470/dampened-amphetamine-stimulated-behavior-and-altered-dopamine-transporter-function-in-the-absence-of-brain-gdnf
#4
Jaakko Kopra, Anne Panhelainen, Sara Af Bjerkén, Lauriina Porokuokka, Kärt Varendi, Soophie Olfat, Heidi Montonen, T Petteri Piepponen, Mart Saarma, Jaan-Olle Andressoo
: Midbrain dopamine neuron dysfunction contributes to various psychiatric and neurological diseases including drug addiction and Parkinson's disease. Because of its well-established dopaminotrophic effects, the therapeutic potential of glial cell line-derived neurotrophic factor (GDNF) has been extensively studied in various disorders with disturbed dopamine homeostasis. The outcomes from pre-clinical and clinical studies vary, however, highlighting a need for a better understanding of the physiological role of GDNF on striatal dopaminergic function...
January 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28078613/l-f001-a-multifunction-rock-inhibitor-prevents-6-ohda-induced-cell-death-through-activating-akt-gsk-3beta-and-nrf2-ho-1-signaling-pathway-in-pc12-cells-and-attenuates-mptp-induced-dopamine-neuron-toxicity-in-mice
#5
Liting Luo, Jingkao Chen, Dan Su, Meihui Chen, Bingling Luo, Rongbiao Pi, Lan Wang, Wei Shen, Rikang Wang
Amounting evidences demonstrated that Rho/Rho-associated kinase (ROCK) might be a novel target for the therapy of Parkinson's disease (PD). Recently, we synthesized L-F001 and revealed it was a potent ROCK inhibitor with multifunctional effects. Here we investigated the effects of L-F001 in PD models. We found that L-F001 potently attenuated 6-OHDA-induced cytotoxicity in PC12 cells and significantly decreased intracellular reactive oxygen species (ROS), prevented the 6-OHDA-induced decline of mitochondrial membrane potential and intracellular GSH levels...
January 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28067625/pituitary-adenylate-cyclase-activating-polypeptide-pacap-has-neuroprotective-function-in-dopamine-based-neurodegeneration-developed-in-two-parkinsonian-models
#6
G Maasz, Z Zrinyi, D Reglodi, D Petrovics, A Rivnyak, T Kiss, A Jungling, A Tamas, Z Pirger
It has been observed that pituitary-adenylate cyclase activating polypeptide (PACAP) rescued DAergic neurons from neurodegeneration and improved motor alterations induced by 6-hydroxy-dopamine (6-OHDA) in rat parkinsonian models. Recently we investigated the molecular background of the neuroprotective effect of PACAP in DA-based neurodegeneration using rotenone-induced snail and 6-OHDA-induced rat models of Parkinson's disease. The behavioural activity, monoamine (DA and serotonin), metabolic enzyme (S-COMT, MB-COMT and MAO-B) and PARK7/DJ-1 protein contents were measured before and after PACAP-treatment in both models...
December 22, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28067072/drug-target-identification-at-the-crossroad-of-neuronal-apoptosis-and-survival
#7
Barbara Maino, Simona Paparone, Cinzia Severini, Maria Teresa Ciotti, Velia D'Agata, Pietro Calissano, Sebastiano Cavallaro
Inappropriate activation of apoptosis may contribute to neurodegeneration, a multifaceted process that results in various chronic disorders, including Alzheimer's and Parkinson's diseases. Several in vitro and in vivo studies demonstrated that neuronal apoptosis is a multi-pathway cell-death program that requires RNA synthesis. Thus, transcriptionally activated genes whose products induce cell death can be triggered by different stimuli and antagonized by neurotrophic factors. Systems biology is now unveiling the series of intracellular signaling pathways and key drug targets at the intersection of neuronal apoptosis and survival...
January 8, 2017: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/28060896/isobavachalcone-attenuates-mptp-induced-parkinson-s-disease-in-mice-by-inhibition-of-microglial-activation-through-nf-%C3%AE%C2%BAb-pathway
#8
Haoran Jing, Shaoxia Wang, Min Wang, Wenliang Fu, Chao Zhang, Donggang Xu
Parkinson's disease (PD) is a complex multi-system and age-related neurodegenerative disorder. The intervention targeting neuroinflammation in PD patients is one effective strategy to slow down or inhibit disease progression. Microglia-mediated inflammatory response plays an important role in Parkinson's, Alzheimer's and other cerebral diseases. Isobavachalcone is a main component of Chinese herb medicine Psoralea corylifolia, which function includes immunoregulation, anti-oxidation and the regulation of β-amyloid (Aβ42) deposited in hippocampus in Alzheimer's patients...
2017: PloS One
https://www.readbyqxmd.com/read/28025780/exosomes-in-parkinson-s-disease
#9
REVIEW
Xiaoqing Wu, Tingting Zheng, Baorong Zhang
Exosomes, nano-sized extracellular vesicles secreted by most cell types, are found in all kinds of biological fluids and tissues, including the central nervous system (CNS). The proposed functions of these vesicles include roles in cell-cell signaling, removal of cellular debris, and transfer of pathogens between cells. Many studies have revealed that exosomes derived from the CNS occur in the cerebrospinal fluid and peripheral body fluids, and their contents are altered during disease, making them an appealing target for biomarker development in Parkinson's disease (PD)...
December 26, 2016: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28024798/zonisamide-attenuates-lactacystin-induced-parkinsonism-in-mice-without-affecting-system-xc
#10
Eduard Bentea, Joeri Van Liefferinge, Lise Verbruggen, Katleen Martens, Sho Kobayashi, Lauren Deneyer, Thomas Demuyser, Giulia Albertini, Katrien Maes, Hideyo Sato, Ilse Smolders, Jan Lewerenz, Ann Massie
Zonisamide (ZNS), an anticonvulsant drug exhibiting symptomatic effects in Parkinson's disease (PD), was recently reported to exert neuroprotection in rodent models. One of the proposed neuroprotective mechanisms involves increased protein expression of xCT, the specific subunit of the cystine/glutamate antiporter system xc(-), inducing glutathione (GSH) synthesis. Here, we investigated the outcome of ZNS treatment in a mouse model of PD based on intranigral proteasome inhibition, and whether the observed effects would be mediated by system xc(-)...
December 24, 2016: Experimental Neurology
https://www.readbyqxmd.com/read/28009769/movement-disorders-induced-by-the-atypical-antipsychotic-aripiprazole
#11
Karim Selfani, Valérie L Soland, Sylvain Chouinard, Philippe Huot
OBJECTIVES: Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors. Because of its partial agonist activity, it was believed that aripiprazole would be less susceptible than typical antipsychotics to induce extrapyramidal side effects. However, a few case-reports and case-series detailing aripiprazole-induced movement disorders have been published, suggesting that aripiprazole-induced movement disorders may arise. Here, we seek to report further cases of aripiprazole-induced movement disorders to raise the awareness of clinicians on this adverse effect...
January 2017: Neurologist
https://www.readbyqxmd.com/read/28004277/tauroursodeoxycholic-bile-acid-arrests-axonal-degeneration-by-inhibiting-the-unfolded-protein-response-in-x-linked-adrenoleukodystrophy
#12
Nathalie Launay, Montserrat Ruiz, Laia Grau, Francisco J Ortega, Ekaterina V Ilieva, Juan José Martínez, Elena Galea, Isidre Ferrer, Erwin Knecht, Aurora Pujol, Stéphane Fourcade
The activation of the highly conserved unfolded protein response (UPR) is prominent in the pathogenesis of the most prevalent neurodegenerative disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), which are classically characterized by an accumulation of aggregated or misfolded proteins. This activation is orchestrated by three endoplasmic reticulum (ER) stress sensors: PERK, ATF6 and IRE1. These sensors transduce signals that induce the expression of the UPR gene programme...
December 21, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28003662/polyanionic-cyclodextrin-induced-supramolecular-nanoparticle
#13
He-Lue Sun, Ying-Ming Zhang, Yong Chen, Yu Liu
Ionizable cyclodextrins have attracted increasing attention in host-guest chemistry and pharmaceutical industry, mainly due to the introduction of favorable electrostatic interactions. The ionizable cyclodextrins could not only enhance its own solubility but also induce oppositely charged guests to form more stable complex. However, the aggregation induced by charged cyclodextrins has rarely been reported. In this work, guided by the concept of molecular-induced aggregation, a series of carboxyl modified cyclodextrins were synthesized via "click" and hydrolysis reaction...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27986997/risk-of-parkinsonism-induced-by-flunarizine-or-cinnarizine-a-population-based-study
#14
Hsiu-Li Lin, Hsiu-Chen Lin, Yuan-Fu Tseng, Shih-Chang Chen, Chien-Yeh Hsu
PURPOSE: This retrospective cohort study used a population-based dataset to test the risk for parkinsonism in patients receiving flunarizine and cinnarizine, compared with matched controls. METHODS: Data were obtained from the National Health Insurance Research Dataset of Taiwan. Patients receiving flunarizine or cinnarizine for more than 1 month between 2000 and 2005 were enrolled. Exclusion criteria included receiving flunarizine, cinnarizine, or antipsychotics for more than 1 month during 1997-1999, a history of neurodegenerative diseases, and an age of less than 30 years...
December 16, 2016: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27981510/aberrant-cpg-methylation-mediates-abnormal-transcription-of-mao-a-induced-by-acute-and-chronic-l-3-4-dihydroxyphenylalanine-administration-in-sh-sy5y-neuronal-cells
#15
Zhaofei Yang, Xuan Wang, Jian Yang, Min Sun, Yong Wang, Xiaomin Wang
L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective drug for therapy of Parkinson's disease (PD); however, long-term use of it causes serious side effects. L-dopa-induced dyskinesia (LID) has consistently been related to L-dopa-derived excessive dopamine release, but the mechanisms have not been addressed very clear. Monoamine oxidase A (MAO-A) is one of the key enzymes in dopamine metabolism and therefore may be involved in L-dopa-induced side effects. And, epigenetic modification controls MAO-A gene transcription...
December 15, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27981499/direct-conversion-of-somatic-cells-into-induced-neurons
#16
REVIEW
Na An, Huiming Xu, Wei-Qiang Gao, Hao Yang
The progressive loss and degeneration of neurons in the central nervous system (CNS), as a result of traumas or diseases including Alzheimer's, Parkinson's, Huntington's disease, stroke, and traumatic injury to the brain and spinal cord, can usually have devastating effects on quality of life. The current strategies available for treatments are described including drug delivery, surgery, electrical stimulation, and cell-based tissue engineering approaches. However, apart from cell-based therapy, other attempts are limited in improving clinical outcomes...
December 16, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27980114/sodium-pumps-mediate-activity-dependent-changes-in-mammalian-motor-networks
#17
Laurence D Picton, Filipe Nascimento, Matthew J Broadhead, Keith T Sillar, Gareth B Miles
: Ubiquitously expressed sodium pumps are best known for maintaining the ionic gradients and resting membrane potential required for generating action potentials. However, activity- and state-dependent changes in pump activity can also influence neuronal firing and regulate rhythmic network output. Here we demonstrate that changes in sodium pump activity regulate locomotor networks in the spinal cord of neonatal mice. The sodium pump inhibitor, ouabain, increased the frequency and decreased the amplitude of drug-induced locomotor bursting, effects which were dependent on the presence of the neuromodulator dopamine...
December 15, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27979722/apomorphine-pharmacological-properties-and-clinical-trials-in-parkinson-s-disease
#18
Peter Jenner, Regina Katzenschlager
Apomorphine is often considered an archetypal dopamine agonist used in the treatment of Parkinson's disease (PD). However, it can be clearly differentiated from most other commonly used dopamine agonists on the basis of its pharmacology and on its unique clinical profile. Like levodopa and dopamine, apomorphine acts as a potent, direct and broad spectrum dopamine agonist activating all dopamine receptor subtypes. It also has affinity for serotonin receptors, and α-adrenergic receptors. Apomorphine is usually titrated to a dose that provides an equivalent antiparkinsonian response to that provided by levodopa, and its subcutaneous delivery allows a rapid onset of action, usually within 7-10 min...
December 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27964831/oculogyric-crises-etiology-pathophysiology-and-therapeutic-approaches
#19
REVIEW
Ewgenia Barow, Susanne A Schneider, Kailash P Bhatia, Christos Ganos
Oculogyric crisis (OGC) describes the clinical phenomenon of sustained dystonic, conjugate and typically upward deviation of the eyes lasting from seconds to hours. It was initially observed in patients with postencephalitic parkinsonism, but since then a number of conditions have been associated with OGC. These include drug-induced reactions, hereditary and sporadic movement disorders, and focal brain lesions. Here, we systematically review the literature and discuss the spectrum of disorders associated with OGC in order to aid clinicians place this rare but distinctive clinical sign into the appropriate diagnostic context...
November 23, 2016: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/27956235/valproic-acid-protects-against-mpp-mediated-neurotoxicity-in-sh-sy5y-cells-through-autophagy
#20
Y Zhang, J Y Wu, L H Weng, X X Li, L J Yu, Y Xu
Autophagy is a common physiological activity in cells. Studies show that dysregulation of autophagy is involved in the pathogenesis of Parkinson's disease (PD). As a commonly used anti-epileptic drug, valproic acid (VPA) has shown neuroprotective effects in PD. The aim of this study was to explore whether the autophagy induced by VPA involved in the neuroprotective effects in PD cell model. We found that VPA treatment counteracted MPP(+)-caused autophagic flux impairment. Forthermore, VPA could alleviates apoptosis, reduce reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) loss caused by MPP(+)...
December 9, 2016: Neuroscience Letters
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