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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/28293168/modeling-human-neurological-and-neurodegenerative-diseases-from-induced-pluripotent-stem-cells-to-neuronal-differentiation-and-its-applications-in-neurotrauma
#1
REVIEW
Hisham Bahmad, Ola Hadadeh, Farah Chamaa, Katia Cheaito, Batoul Darwish, Ahmad-Kareem Makkawi, Wassim Abou-Kheir
With the help of several inducing factors, somatic cells can be reprogrammed to become induced pluripotent stem cell (iPSCs) lines. The success is in obtaining iPSCs almost identical to embryonic stem cells (ESCs), therefore various approaches have been tested and ultimately several ones have succeeded. The importance of these cells is in how they serve as models to unveil the molecular pathways and mechanisms underlying several human diseases, and also in its potential roles in the development of regenerative medicine...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28292181/synthesis-structure-characterization-and-evaluation-in-microglia-cultures-of-neuromelanin-analogues-suitable-for-modeling-parkinson-s-disease
#2
Emanuele Ferrari, Andrea Capucciati, Ilaria Prada, Fabio Andrea Zucca, Giulia D'Arrigo, Daniele Pontiroli, Maria Grazia Bridelli, Michela Sturini, Luigi Bubacco, Enrico Monzani, Claudia Verderio, Luigi Zecca, Luigi Casella
In the substantia nigra of human brain, neuromelanin (NM) released by degenerating neurons can activate microglia with consequent neurodegeneration, typical of Parkinson's disease (PD). Synthetic analogues of NM were prepared to develop a PD model reproducing the neuropathological conditions of the disease. Soluble melanin-protein conjugates were obtained by melanization of fibrillated β-lactoglobulin (fLG). The melanic portion of the conjugates contains either eumelanic (EufLG) or mixed eumelanic/pheomelanic composition (PheofLG), the latter better simulating natural NMs...
March 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28291352/understanding-the-molecular-determinant-of-reversible-human-monoamine-oxidase-b-inhibitors-containing-2h-chromen-2-one-core-structure-based-and-ligand-based-derived-3-d-qsar-predictive-models
#3
Milan Mladenovic, Alexandros Patsilinakos, Adele Pirolli, Manuela Sabatino, Rino Ragno
Monoamine oxidase B (MAO B) catalyzes the oxidative deamination of aryalkylamines neurotransmitters with concomitant reduction of oxygen to hydrogen peroxide. Consequently, the enzyme's malfunction can induce oxidative damage to mitochondrial DNA and mediates development of Parkinson's disease. Thus, MAO B emerges as a promising target for developing pharmaceuticals potentially useful to treat this vicious neurodegenerative condition. Aiming to contribute to the development of drugs with the reversible mechanism of MAO B inhibition only, herein, an extended in silico-in vitro procedure for the selection of novel MAO B inhibitors is demonstrated, including: (1) definition of optimized and validated structure-based (SB) 3-D QSAR models derived from available co-crystallized inhibitor-MAO B complexes; (2) elaboration of structure-activity relationships (SAR) features for either irreversible or reversible MAO B inhibitors to characterize and improve coumarin-based inhibitor activity (Protein Data Bank ID: 2V61) as the most potent reversible lead compound; (3) definition of structure-based (SB) and ligand-based (LB) alignment rules assessments by which virtually any untested potential MAO B inhibitor might be evaluated; (4) predictive ability validation of the best 3-D QSAR model through SB/LB modeling of four coumarin-based external test sets (267 compounds); (5) design and SB/LB alignment of novel coumarin-based scaffolds experimentally validated through synthesis and biological evaluation in vitro...
March 14, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28286180/dysregulation-of-bet-proteins-in-levodopa-induced-dyskinesia
#4
David A Figge, David G Standaert
Levodopa (L-DOPA) remains the most effective pharmacological treatment for Parkinson Disease (PD) but its use is limited by the development of debilitating drug-related side effects, particularly L-DOPA induced dyskinesia (LID). LID is a consequence of long-term L-DOPA use, and in model systems is characterized by a "priming effect", whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent dopaminergic stimulation. Preliminary studies into the mechanisms underlying this cellular memory have indicated an important role for epigenetic change but many of the downstream mechanisms remain unknown...
March 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28284907/minocycline-protects-rescues-and-prevents-knockdown-transgenic-parkin-drosophila-against-paraquat-iron-toxicity-implications-for-autosomic-recessive-juvenile-parkinsonism
#5
Hector Flavio Ortega-Arellano, Marlene Jimenez-Del-Rio, Carlos Velez-Pardo
Autosomal recessive Juvenile Parkinsonism (AR-JP) is a chronic, progressive neurodegenerative disorder caused by mutation in the PARKIN gene, and invariably associated with dopaminergic (DAergic) neuronal loss and brain iron accumulation. Since current medical therapy is symptomatic and lacks significant disease-modifying effects, other treatment approaches are urgently needed it. In the present work, we investigate the role of minocycline (MC) in paraquat (PQ)/iron-induced neurotoxicity in the Drosophila TH > parkin-RNAi/+ (w[*]; UAS-parkin-RNAi; TH-GAL4) fly and have shown the following: (i) MC increased life span and restored the locomotor activity of knockdown (KD) transgenic parkin flies in comparison with the control (vehicle) group; (ii) MC at low (0...
March 8, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28284817/differential-effects-of-gaseous-versus-injectable-anesthetics-on-changes-in-regional-cerebral-blood-flow-and-metabolism-induced-by-l-dopa-in-a-rat-model-of-parkinson-s-disease
#6
Zisis Bimpisidis, Carl M Öberg, Natallia Maslava, M Angela Cenci, Cornelia Lundblad
Preclinical imaging of brain activity requires the use of anesthesia. In this study, we have compared the effects of two widely used anesthetics, inhaled isoflurane and ketamine/xylazine cocktail, on cerebral blood flow and metabolism in a rat model of Parkinson's disease and l-DOPA-induced dyskinesia. Specific tracers were used to estimate regional cerebral blood flow (rCBF - [(14)C]-iodoantipyrine) and regional cerebral metabolic rate (rCMR - [(14)C]-deoxyglucose) with a highly sensitive autoradiographic method...
March 8, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28276260/holothuria-scabra-extracts-exhibit-anti-parkinson-potential-in-c-elegans-a-model-for-anti-parkinson-testing
#7
Pawanrat Chalorak, Prapaporn Jattujan, Saksit Nobsathian, Tanate Poomtong, Prasert Sobhon, Krai Meemon
OBJECTIVES: Parkinson's disease (PD) is associated with aggregation of α-synuclein and selective death of dopaminergic (DA) neurons in the substantia nigra, thereby leading to cognitive and motor impairments. Nowadays, the drugs commonly used for PD treatment, such as levodopa, provide only symptomatic relief. Therefore, seeking new drugs against PD, especially from plants and marine organisms, is one of the major research areas to be explored. This study aimed to investigate the anti-Parkinson activity of the extracts from the sea cucumber, Holothuria scabra, by using Caenorhabditis elegans as a model...
March 9, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28275911/sigma-1-%C3%AF-1-receptor-in-memory-and-neurodegenerative-diseases
#8
Tangui Maurice, Nino Goguadze
The sigma-1 (σ1) receptor has been associated with regulation of intracellular Ca(2+) homeostasis, several cellular signaling pathways, and inter-organelle communication, in part through its chaperone activity. In vivo, agonists of the σ1 receptor enhance brain plasticity, with particularly well-described impact on learning and memory. Under pathological conditions, σ1 receptor agonists can induce cytoprotective responses. These protective responses comprise various complementary pathways that appear to be differentially engaged according to pathological mechanism...
March 9, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28273839/parkinson-s-disease-from-pathogenesis-to-pharmacogenomics
#9
REVIEW
Ramón Cacabelos
Parkinson's disease (PD) is the second most important age-related neurodegenerative disorder in developed societies, after Alzheimer's disease, with a prevalence ranging from 41 per 100,000 in the fourth decade of life to over 1900 per 100,000 in people over 80 years of age. As a movement disorder, the PD phenotype is characterized by rigidity, resting tremor, and bradykinesia. Parkinson's disease -related neurodegeneration is likely to occur several decades before the onset of the motor symptoms. Potential risk factors include environmental toxins, drugs, pesticides, brain microtrauma, focal cerebrovascular damage, and genomic defects...
March 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28264738/the-dark-side-of-dopaminergic-therapies-in-parkinson-s-disease-shedding-light-on-aberrant-salience
#10
Michele Poletti
Psychotic subjects and patients with Parkinson's disease (PD) "on" dopaminergic drugs, especially on dopamine agonists, present a hyperdopaminergic state that interferes with learning processing. These clinical populations present with distinct alterations of learning that share an increased potential motivational significance of stimuli: psychotic subjects may attribute salience to neutral stimuli, while medicated PD patients may overvalue rewards. Herein is discussed the speculative hypothesis that the hyperdopaminergic state induced by dopaminergic treatments, especially with dopamine agonists, may also facilitate the attribution of salience to neutral stimuli in PD patients, altering the physiological attribution of salience...
March 7, 2017: CNS Spectrums
https://www.readbyqxmd.com/read/28264466/synthesis-and-characterization-of-a-new-bivalent-ligand-combining-caffeine-and-docosahexaenoic-acid
#11
Víctor Fernández-Dueñas, Jhonny Azuaje, Xavier Morató, Begoña Cordobilla, Joan Carles Domingo, Eddy Sotelo, Francisco Ciruela
Caffeine is a promising drug for the management of neurodegenerative diseases such as Parkinson's disease (PD), demonstrating neuroprotective properties that have been attributed to its interaction with the basal ganglia adenosine A2A receptor (A2AR). However, the doses needed to exert these neuroprotective effects may be too high. Thus, it is important to design novel approaches that selectively deliver this natural compound to the desired target. Docosahexaenoic acid (DHA) is the major omega-3 fatty acid in the brain and can act as a specific carrier of caffeine...
February 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28263159/-dyskinesia-in-parkinson-s-disease-an-update-on-new-neuroimaging-methods-and-treatment-possibilities
#12
Birgitte Liang Chen Thomsen, Damian Marc Herz, Hartwig Roman Siebner, Annemette Løkkegaard
Levodopa-induced dyskinesia (LID) represents a severe adverse effect of long-term treatment of Parkinson's disease with levodopa. Neuroimaging studies have contributed to our understanding of LID and may help to identify patients at risk of developing LID. Amantadine can be used for the treatment of LID, and novel drugs are under development. Deep brain stimulation of the subthalamic nucleus and globus pallidus internus alleviates LID, the former indirectly by reducing levodopa intake, the latter through direct effects...
March 6, 2017: Ugeskrift for Laeger
https://www.readbyqxmd.com/read/28260906/contemplating-stem-cell-therapy-for-epilepsy-induced-neuropsychiatric-symptoms
#13
REVIEW
Gautam Rao, Sherwin Mashkouri, David Aum, Paul Marcet, Cesar V Borlongan
Epilepsy is a debilitating disease that impacts millions of people worldwide. While unprovoked seizures characterize its cardinal symptom, an important aspect of epilepsy that remains to be addressed is the neuropsychiatric component. It has been documented for millennia in paintings and literature that those with epilepsy can suffer from bouts of aggression, depression, and other psychiatric ailments. Current treatments for epilepsy include the use of antiepileptic drugs and surgical resection. Antiepileptic drugs reduce the overall firing of the brain to mitigate the rate of seizure occurrence...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28258522/sitagliptin-and-liraglutide-reversed-nigrostriatal-degeneration-of-rodent-brain-in-rotenone-induced-parkinson-s-disease
#14
Ghada A Badawi, Mai A Abd El Fattah, Hala F Zaki, Moushira I El Sayed
The present study investigated the possible relationship between pro-inflammatory cytokines and programmed nigral neuronal death in rotenone model of Parkinson's disease (PD). Sitagliptin and liraglutide efficacy to inhibit the inflammatory-apoptotic degenerative process were investigated, too. The experimental PD were induced in male albino rats by ten subcutaneously injections of rotenone (3 mg/kg/day, s.c). All treatment drugs were administered for 16 days after induction of Parkinson rat's model. Sitagliptin and liraglutide were administered in three different dose levels (10-20-30 mg/kg, p...
March 4, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28257461/quantitative-analysis-of-the-therapeutic-effect-of-magnolol-on-mptp-induced-mouse-model-of-parkinson-s-disease-using-in-vivo-18f-9-fluoropropyl-dihydrotetrabenazine-pet-imaging
#15
Chi-Chang Weng, Zi-An Chen, Ko-Ting Chao, Ting-Wei Ee, Kun-Ju Lin, Ming-Huan Chan, Ing-Tsung Hsiao, Tzu-Chen Yen, Mei-Ping Kung, Ching-Han Hsu, Shiaw-Pyng Wey
18F-9-Fluoropropyl-(+)-dihydrotetrabenazine [18F-FP-(+)-DTBZ] positron emission tomography (PET) has been shown to detect dopaminergic neuron loss associated with Parkinson's disease (PD) in human and neurotoxin-induced animal models. A polyphenol compound, magnolol, was recently proposed as having a potentially restorative effect in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 6-hydroxydopamine-treated animal models. In this study, 18F-FP-(+)-DTBZ PET was used to determine the therapeutic efficacy of magnolol in an MPTP-PD mouse model that was prepared by giving an intraperitoneally (i...
2017: PloS One
https://www.readbyqxmd.com/read/28256010/striatal-d1-medium-spiny-neuron-activation-induces-dyskinesias-in-parkinsonian-mice
#16
Xiomara A Perez, Danhui Zhang, Tanuja Bordia, Maryka Quik
BACKGROUND: Dyskinesias are a disabling motor complication that arises with prolonged l-dopa treatment. Studies using D1 receptor drugs and genetically modified mice suggest that medium spiny neurons expressing D1 receptors play a primary role in l-dopa-induced dyskinesias. However, the specific role of these neurons in dyskinesias is not fully understood. METHODS: We used optogenetics, which allows for precise modulation of select neurons in vivo, to investigate whether striatal D1-expressing medium spiny neuron activity regulates abnormal involuntary movements or dyskinesia in parkinsonian mice...
March 3, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28253983/micrornas-aging-cellular-senescence-and-alzheimer-s-disease
#17
P H Reddy, J Williams, F Smith, J S Bhatti, S Kumar, M Vijayan, R Kandimalla, C S Kuruva, R Wang, M Manczak, X Yin, A P Reddy
Aging is a normal process of living being. It has been reported that multiple cellular changes, including oxidative damage/mitochondrial dysfunction, telomere shortening, inflammation, may accelerate the aging process, leading to cellular senescence. These cellular changes induce age-related human diseases, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, cardiovascular, cancer, and skin diseases. Changes in somatic and germ-line DNA and epigenetics are reported to play large roles in accelerating the onset of human diseases...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28253352/dopamine-d2-receptor-and-%C3%AE-arrestin-2-mediate-amyloid-%C3%AE-elevation-induced-by-anti-parkinson-s-disease-drugs-levodopa-and-piribedil-in-neuronal-cells
#18
Jing Lu, Xiaohang Li, Qinying Wang, Gang Pei
Although levodopa is the first-line medication for the treatment of Parkinson's disease (PD) showing unsurpassable efficiency, its chronic use causes dyskinesia. Accordingly, dopamine agonists are increasingly employed as monotherapy or in combination with levodopa to reduce the risk of motor complications. It is well recognized that patients with PD often exhibit cognitive deficits. However, clinical and animal studies assessing the effects of dopaminergic medications on cognition are controversial. Amyloid-β (Aβ) is one of the major hallmarks of Alzheimer's disease (AD), leading to progressive memory loss and cognitive deficit...
2017: PloS One
https://www.readbyqxmd.com/read/28244186/cerebrospinal-fluid-levels-of-catecholamines-and-its-metabolites-in-parkinson-s-disease-effect-of-l-dopa-treatment-and-changes-in-levodopa-induced-dyskinesia
#19
A D Andersen, M Blaabjerg, M Binzer, A Kamal, H Thagesen, T W Kjaer, E Stenager, J B Gramsbergen
Levodopa (L-DOPA, L-3,4-dihydroxyphenylalanine) is the most effective drug in the symptomatic treatment of Parkinson's disease (PD), but chronic use initiates a maladaptive process leading to L-DOPA-induced dyskinesia (LID). Risk factors for early onset LID include younger age, more severe disease at baseline and higher daily L-DOPA dose, but biomarkers to predict the risk of motor complications are not yet available. Here we investigated whether CSF levels of catecholamines and its metabolites are altered in PD patients with LID (PD-LID, n=8)) as compared to non-dyskinetic PD patients receiving L-DOPA (PD-L, n=6), or not receiving L-DOPA (PD-N, n=7) as well as non-PD controls (n=16)...
February 28, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28242362/intravenous-administration-of-mitochondria-for-treating-experimental-parkinson-s-disease
#20
Xianxun Shi, Ming Zhao, Chen Fu, Ailing Fu
Mitochondrial dysfunction is associated with a large number of human diseases, including neurological and muscular degeneration, cardiovascular disorders, obesity, diabetes, aging and rare mitochondrial diseases. Replacement of dysfunctional mitochondria with functional exogenous mitochondria is proposed as a general principle to treat these diseases. Here we found that mitochondria isolated from human hepatoma cell could naturally enter human neuroblastoma SH-SY5Y cell line, and when the mitochondria were intravenously injected into mice, all of the mice were survived and no obvious abnormality appeared...
February 24, 2017: Mitochondrion
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