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Drug induced parkinsonism

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https://www.readbyqxmd.com/read/29027056/curcumin-affords-neuroprotection-and-inhibits-%C3%AE-synuclein-aggregation-in-lipopolysaccharide-induced-parkinson-s-disease-model
#1
Neha Sharma, Bimla Nehru
Parkinson's disease (PD) pathology is characterized by the abnormal accumulation and aggregation of the pre-synaptic protein α-synuclein in the dopaminergic neurons as Lewy bodies (LBs). Curcumin, which plays a neuroprotective role in various animal models of PD, was found to directly modulate the aggregation of α-synuclein in in vitro as well as in in vivo studies. While curcumin has been shown to exhibit strong anti-oxidant and anti-inflammatory properties, there are a number of other possible mechanisms by which curcumin may alter α-synuclein aggregation which still remains obscure...
October 12, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/29019394/studies-on-16-17-pyrazoline-substituted-heterosteroids-as-anti-alzheimer-and-anti-parkinsonian-agents-using-lps-induced-neuroinflammation-models-of-mice-and-rats
#2
Ranjit Singh, Sridhar Thota, Ranju Bansal
Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common forms of neurodegenerative disorders. Dehydroepiandrosterone (DHEA) has been reported as a neuroprotective steroid useful in the therapeutic management of neurodegenerative disorders such as AD and PD. Herein we report the synthesis and evaluation of a new series of 16,17-pyrazolinyl DHEA analogues 2-4a-d as neuroprotective agents using LPS-induced neuroinflammation animal models. Treatment with the pyrazoline substituted steroids considerably improved the LPS-induced learning, memory and movement deficits in animal models...
October 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29017011/altered-volatile-organic-compounds-profile-in-transgenic-rats-bearing-a53t-mutation-of-human-alpha-synuclein-comparison-with-dopaminergic-and-serotonergic-denervation
#3
John P M Finberg, Yuval Aluf, Yelena Loboda, Morad K Nakhleh, Raneen Jeries, Manal Aboud, Salman Zubedat, Avi Avital, Soliman Khatib, Jacob Vaya, Hossam Haick
Early diagnosis of Parkinson's disease (PD) is of great importance due its progressive phenotype. Neuroprotective drugs could potentially slow down disease progression if used at early stages. Previously, we have reported an altered content of volatile organic compounds (VOCs) in the breath of rats following a 50% reduction in striatal dopamine (DA) content induced by 6-hydroxydopamine. We now report on the difference in the breath-print and content of VOCs between rats with mild and severe lesions of DA neurons, serotonergic neuronal lesions, and transgenic (Tg) rats carrying the PD-producing A53T mutation of the SNCA (alpha-synuclein) gene...
October 10, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28984087/effects-of-rhei-undulati-rhizoma-on-lipopolysaccharide-induced-neuroinflammation-in-vitro-and-in-vivo
#4
Deok-Sang Hwang, Pil Sung Gu, Namkwon Kim, Young Pyo Jang, Myung Sook Oh
Neuroinflammation plays a critical role in the pathogenesis of degenerative brain diseases such as Alzheimer's disease and Parkinson's disease. Microglia are the major components of the brain immune system that regulate inflammatory processes. Activated microglia release pro-inflammatory factors and cytokines, resulting in neuronal cell death. We focused on inhibiting the activation of microglia from a stimulus as a strategy to search for neuroprotective drugs. Rhei Undulati Rhizoma (RUR) is traditionally used to treat various inflammatory disorders...
October 6, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28973645/alpha-synuclein-induces-the-unfolded-protein-response-in-parkinson-s-disease-snca-triplication-ipsc-derived-neurons
#5
Sabrina M Heman-Ackah, Raquel Manzano, Jeroen J M Hoozemans, Wiep Scheper, Rowan Flynn, Wilfried Haerty, Sally A Cowley, Andrew R Bassett, Matthew J A Wood
The recent generation of induced pluripotent stem cells (iPSCs) from a patient with Parkinson's disease (PD) resulting from triplication of the α-synuclein (SNCA) gene locus allows unprecedented opportunities to explore its contribution to the molecular pathogenesis of PD. We used the double-nicking CRISPR/Cas9 system to conduct site-specific mutagenesis of SNCA in these cells, generating an isogenic iPSC line with normalized SNCA gene dosage. Comparative gene expression analysis of neuronal derivatives from these iPSCs revealed an ER stress phenotype, marked by induction of the IRE1α/XBP1 axis of the unfolded protein response (UPR) and culminating in terminal UPR activation...
September 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28955204/impairment-of-serotonergic-transmission-by-the-antiparkinsonian-drug-l-dopa-mechanisms-and-clinical-implications
#6
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/28952832/prevalence-and-pattern-of-antipsychotic-induced-movement-disorders-in-a-tertiary-care-teaching-hospital-in-india-a-cross-sectional-study
#7
Nimisha Desai, Parvati B Patel, Sandip Shah, Tejas K Patel, Saurabh N Shah, Ela Vatsala
OBJECTIVES: To assess prevalence and pattern of movement disorders among patients taking antipsychotic medications. METHODS: This cross-sectional, intensive monitoring (patient interview, case record form review and clinical examination) study was conducted in patients taking antipsychotic drugs irrespective of duration for the development of movement disorders. The psychiatrist used Modified Simpson-Angus Scale score (10-item scale), Barnes' rating scale and Abnormal Involuntary Movement Scale to diagnose parkinsonism, akathisia and tardive dyskinesia, respectively...
September 27, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28928221/upregulation-of-autophagy-related-gene-5-protects-dopaminergic-neurons-in-a-zebrafish-model-of-parkinson-s-disease
#8
Zhan-Ying Hu, Bo Chen, Jing-Pu Zhang, Yuan-Yuan Ma
Parkinson's disease (PD) is one of the most epidemic neurodegenerative diseases, and is characterized by movement disorders arising from loss of midbrain dopaminergic (DA) neurons. Recently, the relationship between PD and autophagy has received considerable attention, but information about the mechanisms involved is lacking. Here, we report that autophagy-related gene 5 (ATG5) is potentially important in protecting dopaminergic neurons in a 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model in zebrafish...
September 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28922189/acr-acnm-practice-parameter-for-the-performance-of-dopamine-transporter-dat-single-photon-emission-computed-tomography-spect-imaging-for-movement-disorders
#9
Rathan M Subramaniam, Kirk A Frey, Christopher H Hunt, Gustavo A Mercier, Lilja B Solnes, Patrick M Colletti, Yang Lu, Bital Savir-Baruch, Hadyn T Williams
This American College of Radiology and American College of Nuclear Medicine joint clinical practice parameter is for performance of dopamine transporter single photon emission computed tomography (SPECT) imaging, for patients with movement disorders. Parkinsonian syndrome (PS) consists of a group of neurodegenerative diseases including Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies (DLB). Accurate diagnosis of PS is critical for clinical management...
September 15, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28912301/early-onset-drug-induced-parkinsonism-after-exposure-to-offenders-implies-nigrostriatal-dopaminergic-dysfunction
#10
Seok Jong Chung, Han Soo Yoo, Hyojeong Moon, Jungsu S Oh, Jae Seung Kim, Yong Hee Park, Jin Yong Hong, Byoung Seok Ye, Young H Sohn, Phil Hyu Lee
OBJECTIVES: The onset of parkinsonism in patients with drug-induced parkinsonism (DIP) exhibits extensive individual variability following exposure to offending drugs. We investigated whether the individual variations in the onset time of parkinsonism reflected the underlying subtle dopaminergic dysfunction in DIP. METHODS: We enrolled 71 patients with DIP who had visually normal striatal dopamine transporter (DAT) availability in (18)F-FP-CIT positron emission tomography scans...
September 14, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28904554/plants-derived-neuroprotective-agents-cutting-the-cycle-of-cell-death-through-multiple-mechanisms
#11
REVIEW
Taiwo Olayemi Elufioye, Tomayo Ireti Berida, Solomon Habtemariam
Neuroprotection is the preservation of the structure and function of neurons from insults arising from cellular injuries induced by a variety of agents or neurodegenerative diseases (NDs). The various NDs including Alzheimer's, Parkinson's, and Huntington's diseases as well as amyotropic lateral sclerosis affect millions of people around the world with the main risk factor being advancing age. Each of these diseases affects specific neurons and/or regions in the brain and involves characteristic pathological and molecular features...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28904388/protective-efficacy-of-phosphodiesterase-1-inhibition-against-alpha-synuclein-toxicity-revealed-by-compound-screening-in-luhmes-cells
#12
Matthias Höllerhage, Claudia Moebius, Johannes Melms, Wei-Hua Chiu, Joachim N Goebel, Tasnim Chakroun, Thomas Koeglsperger, Wolfgang H Oertel, Thomas W Rösler, Marc Bickle, Günter U Höglinger
α-synuclein-induced neurotoxicity is a core pathogenic event in neurodegenerative synucleinopathies such as Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. There is currently no disease-modifying therapy available for these diseases. We screened 1,600 FDA-approved drugs for their efficacy to protect LUHMES cells from degeneration induced by wild-type α-synuclein and identified dipyridamole, a non-selective phosphodiesterase inhibitor, as top hit. Systematic analysis of other phosphodiesterase inhibitors identified a specific phosphodiesterase 1 inhibitor as most potent to rescue from α-synuclein toxicity...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28901627/microstructural-white-matter-alterations-in-patients-with-drug-induced-parkinsonism
#13
Yoonju Lee, Yong Ho Choi, Jae Jung Lee, Hye Sun Lee, Young H Sohn, Jong-Min Lee, Phil Hyu Lee
Drug-induced parkinsonism (DIP) is the second most common etiology of parkinsonism. And yet, there is little information on structural imaging in DIP to elucidate the accurate underlying pathomechanisms. To investigate microstructural white matter (WM) in patients with DIP using diffusion tensor image and to determine its relationship to severity of parkinsonian motor symptoms and cognitive function. A total of 42 patients with DIP, 65 with Parkinson's disease, and 33 control subjects were recruited from a movement disorders outpatient clinic...
September 12, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28898256/carbidopa-a-drug-in-use-for-management-of-parkinson-disease-inhibits-t-cell-activation-and-autoimmunity
#14
Huabin Zhu, Henrique Lemos, Brinda Bhatt, Bianca N Islam, Abhijit Singh, Ashish Gurav, Lei Huang, Darren D Browning, Andrew Mellor, Sadanand Fulzele, Nagendra Singh
Carbidopa is a drug that blocks conversion of levodopa to dopamine outside of central nervous system (CNS) and thus inhibits unwanted side effects of levodopa on organs located outside of CNS during management of Parkinson's Disease (PD). PD is associated with increased expression of inflammatory genes in peripheral and central nervous system (CNS), infiltration of immune cells into brain, and increased numbers of activated/memory T cells. Animal models of PD have shown a critical role of T cells in inducing pathology in CNS...
2017: PloS One
https://www.readbyqxmd.com/read/28881378/effects-of-rifampin-on-the-pharmacokinetics-of-a-single-dose-of-istradefylline-in-healthy-subjects
#15
Mayumi Mukai, Tatsuo Uchimura, Xiaoping Zhang, Douglas Greene, Maria Vergeire, Marc Cantillon
Istradefylline, a selective adenosine A2A inhibitor, is under development for the treatment of Parkinson's disease. The effect of oral steady-state rifampin 600 mg/day, a potent cytochrome P450 (CYP) 3A4 inducer, on the disposition of a single oral dose of istradefylline 40 mg was determined in a crossover study in 20 healthy subjects by measuring plasma concentrations of istradefylline and its M1 and M8 metabolites and their derived pharmacokinetic parameters. Based on the geometric mean ratio of log-transformed data, rifampin reduced istradefylline exposure: Cmax , 0...
September 7, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28880414/levodopa-treatment-and-dendritic-spine-pathology
#16
REVIEW
Haruo Nishijima, Tatsuya Ueno, Yukihisa Funamizu, Shinya Ueno, Masahiko Tomiyama
Parkinson's disease (PD) is a neurodegenerative disorder associated with the progressive loss of nigrostriatal dopaminergic neurons. Levodopa is the most effective treatment for the motor symptoms of PD. However, chronic oral levodopa treatment can lead to various motor and nonmotor complications because of nonphysiological pulsatile dopaminergic stimulation in the brain. Examinations of autopsy cases with PD have revealed a decreased number of dendritic spines of striatal neurons. Animal models of PD have revealed altered density and morphology of dendritic spines of neurons in various brain regions after dopaminergic denervation or dopaminergic denervation plus levodopa treatment, indicating altered synaptic transmission...
September 7, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28877525/development-of-a-thai-parkinson-s-disease-screening-tool-and-the-prevalence-of-parkinsonism-and-parkinson-s-disease-based-on-a-community-survey-in-bangkok
#17
Weerasak Muangpaisan, Pitiporn Siritipakorn, Prasert Assantachai
INTRODUCTION: Few epidemiological data of parkinsonism and Parkinson's disease (PD) exist in Southeast Asia. We aimed to develop and validate a screening tool, and investigate the prevalence of parkinsonism and PD via a community survey. METHODS: A PD-screening tool comprising 11 "yes/no" items was developed in a clinical setting and validated in the community. The prevalence of PD and parkinsonism was investigated in a survey that included PD screening tools, face-to-face interviews, and physical examinations...
2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28875428/timed-release-of-cerebrolysin-using-drug-loaded-titanate-nanospheres-reduces-brain-pathology-and-improves-behavioral-functions-in-parkinson-s-disease
#18
Asya Ozkizilcik, Aruna Sharma, Dafin F Muresanu, José V Lafuente, Z Ryan Tian, Ranjana Patnaik, Herbert Mössler, Hari S Sharma
Previous studies from our laboratory show that intraperitoneal injections of 1-metyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP, 20 mg/kg) daily within 2-h intervals for 5 days in mice induce Parkinson's disease (PD)-like symptoms on the 8th day. A significant decrease in dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) along with a marked decrease in the number of tyrosine hydroxylase (TH)-positive cells in the substantia nigra pars compacta (SNpc) and striatum (STr) confirms the validity of this model for studying PD...
September 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28872590/synthesis-of-nitric-oxide-donors-derived-from-piloty-s-acid-and-study-of-their-effects-on-dopamine-secretion-from-pc12-cells
#19
Daniele Sanna, Gaia Rocchitta, Maria Serra, Marcello Abbondio, Pier Andrea Serra, Rossana Migheli, Lidia De Luca, Eugenio Garribba, Andrea Porcheddu
This study investigated the mechanisms and kinetics of nitric oxide (NO) generation by derivatives of Piloty's acid (NO-donors) under physiological conditions. In order to qualitatively and quantitatively measure NO release, electron paramagnetic resonance (EPR) was carried out with NO spin trapping. In addition, voltammetric techniques, including cyclic voltammetry and constant potential amperometry, were used to confirm NO release from Piloty's acid and its derivatives. The resulting data showed that Piloty's acid derivatives are able to release NO under physiological conditions...
September 5, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/28854243/antiparkinsonian-effects-of-the-radiprodil-and-tozadenant-combination-in-mptp-treated-marmosets
#20
Anne Michel, Jean-Marie Nicolas, Sarah Rose, Michael Jackson, Peter Colman, Willy Briône, David Sciberras, Pierandrea Muglia, Dieter K Scheller, Martin Citron, Patrick Downey
OBJECTIVE: Investigate a combination of two clinically tested drugs, the NR2B antagonist Radiprodil and the A2A antagonist Tozadenant in the MPTP-treated marmoset model of Parkinson's Disease (PD). BACKGROUND: In PD, there remains a need for the development of non-dopaminergic drugs to effectively treat the motor symptoms without the induction of L-Dopa-induced motor complications. METHODS: Clinically relevant doses of Radiprodil and Tozadenant were given both alone and in combination without the addition of L-Dopa, and the antiparkinsonian efficacy of the treatments was assessed in a primate model of PD...
2017: PloS One
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