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https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#1
Mariama Jaiteh, Alexey Zeifman, Marcus Saarinen, Per Svenningsson, José M Brea, Maria Isabel Loza, Jens Carlsson
Modulation of multiple biological targets with a single drug can lead to synergistic therapeutic effects and has been demonstrated to be essential for efficient treatment of CNS disorders. However, rational design of compounds that interact with several targets is very challenging. Here, we demonstrate that structure-based virtual screening can guide the discovery of multi-target ligands of unrelated proteins relevant for Parkinson's disease. A library with 5.4 million molecules was docked to crystal structures of the A2A adenosine receptor (A2AAR) and monoamine oxidase B (MAO-B)...
May 24, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29790977/alpha-synuclein-aggregates-in-labial-salivary-glands-of-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#2
Alx Iranzo, Sergi Borrego, Isabel Vilaseca, Carles Martí, Mónica Serradell, Raquel Sánchez-Valle, Gabor G Kovacs, Francesc Valldeoriola, Carles Gaig, Joan Santamaria, Eduard Tolosa, Ellen Gelpi
Study Objectives : To assess whether biopsy of the labial minor salivary glands safely detects phosphorylated alpha-synuclein (pAS) deposits in idiopathic REM sleep behavior disorder (IRBD), a condition that precedes the cardinal manifestations of synuclein disorders associated with Lewy type pathology, namely Parkinson disease (PD) and dementia with Lewy bodies (DLB). Methods: In a prospective study, labial biopsy of the minor salivary glands was performed in 62 IRBD patients, 13 PD and 10 DLB patients who were initially diagnosed with IRBD, and in 33 controls...
May 22, 2018: Sleep
https://www.readbyqxmd.com/read/29790422/autologous-induced-pluripotent-stem-cell-derived-neurons-to-treat-parkinson-s-disease
#3
Jeanne F Loring
In 2012, we planned a program to develop a neuron replacement therapy for Parkinson's disease (PD) that would have the greatest promise to help the patients. PD is a movement disorder caused by the progressive, inevitable loss of a specific type of dopamine neuron in the brain. The only viable treatment to reverse the progress of the disease is to replace those neurons; we decided to make dopamine neurons that matched the patients, by differentiating induced pluripotent stem cells (iPSCs) that we generated from individuals with PD...
May 23, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29786160/aberrant-learning-in-parkinson-s-disease-a-neurocomputational-study-on-bradykinesia
#4
Mauro Ursino, Chiara Baston
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive decline in motor functions, such as bradykinesia, caused by the pathological denervation of nigrostriatal dopaminergic neurons within the basal ganglia (BG). It is acknowledged that dopamine (DA) directly affects the modulatory role of BG towards the cortex. However, a growing body of literature is suggesting that DA induced aberrant synaptic plasticity could play a role in the core symptoms of PD, thus recalling for a "reconceptualization" of the pathophysiology...
May 22, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29786072/mptp-driven-nlrp3-inflammasome-activation-in-microglia-plays-a-central-role-in-dopaminergic-neurodegeneration
#5
Eunju Lee, Inhwa Hwang, Sangjun Park, Sujeong Hong, Boreum Hwang, Yoeseph Cho, Junghyun Son, Je-Wook Yu
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) and the reduction of dopamine levels in the striatum. Although details of the molecular mechanisms underlying dopaminergic neuronal death in PD remain unclear, neuroinflammation is also considered a potent mediator in the pathogenesis and progression of PD. In the present study, we present evidences that microglial NLRP3 inflammasome activation is critical for dopaminergic neuronal loss and the subsequent motor deficits in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29786071/dopamine-d2-receptor-restricts-astrocytic-nlrp3-inflammasome-activation-via-enhancing-the-interaction-of-%C3%AE-arrestin2-and-nlrp3
#6
Jialei Zhu, Zhaoli Hu, Xiaojuan Han, Dongshuo Wang, Qingling Jiang, Jianhua Ding, Ming Xiao, Cong Wang, Ming Lu, Gang Hu
Astrocytes are involved in the neuroinflammation of neurodegenerative diseases, such as Parkinson's disease (PD). Among the numerous inflammatory cytokines, interleukin-1β (IL-1β) produced by astrocytic Nod-like receptor protein (NLRP) inflammasome is crucial in the pathogenesis of PD. β-arrestin2-mediated dopamine D2 receptor (Drd2) signal transduction has been regarded as a potential anti-inflammatory target. Our previous study revealed that astrocytic Drd2 suppresses neuroinflammation in the central nervous system...
May 21, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29785679/drooling-in-parkinson-s-disease-evidence-of-a-role-for-divided-attention
#7
Hannah Reynolds, Nick Miller, Richard Walker
Drooling is a frequently reported symptom in Parkinson's Disease (PD) with significant psychosocial impact and negative health consequences including silent aspiration of saliva with the associated risk of respiratory infections. It is suggested that in PD drooling is associated with inefficient oropharyngeal swallowing which reduces the effective clearance of saliva rather than hyper-salivation. This is compounded by unintended mouth opening and flexed posture increasing anterior loss of saliva. It is reported to occur most frequently during cognitively distracting concurrent tasks suggesting an impact from divided attention in a dual-task situation...
May 21, 2018: Dysphagia
https://www.readbyqxmd.com/read/29785638/intermittent-convection-enhanced-delivery-of-gdnf-into-rhesus-monkey-putamen-absence-of-local-or-cerebellar-toxicity
#8
Matthias Luz, Philip C Allen, John Bringas, Chris Boiko, Diane E Stockinger, Kristen J Nikula, Owen Lewis, Max Woolley, H Christian Fibiger, Krystof Bankiewicz, Erich Mohr
Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions...
May 22, 2018: Archives of Toxicology
https://www.readbyqxmd.com/read/29785199/physical-exercise-for-parkinson-s-disease-clinical-and-experimental-evidence
#9
REVIEW
Alessandro Oliveira de Carvalho, Alberto Souza Sá Filho, Eric Murillo-Rodriguez, Nuno Barbosa Rocha, Mauro Giovanni Carta, Sergio Machado
Background: National projections about the increase in the elderly population over 60 years bring with it an increase in the number of people affected by Parkinson's Disease (PD), making it an important public health problem. Therefore, the establishment of effective strategies for intervention in people with PD needs to be more clearly investigated. Objective: The study aimed to report the effectiveness of exercise on functional capacity and neurobiological mechanisms in people with PD...
2018: Clinical Practice and Epidemiology in Mental Health: CP & EMH
https://www.readbyqxmd.com/read/29784986/a-workflow-for-the-integrative-transcriptomic-description-of-molecular-pathology-and-the-suggestion-of-normalizing-compounds-exemplified-by-parkinson-s-disease
#10
Mohamed Hamed, Yvonne Gladbach, Steffen Möller, Sarah Fischer, Mathias Ernst, Stephan Struckmann, Alexander Storch, Georg Fuellen
The volume of molecular observations on human diseases in public databases is continuously increasing at accelerating rates. A bottleneck is their computational integration into a coherent description, from which researchers may derive new well-founded hypotheses. Also, the need to integrate data from different technologies (genetics, coding and regulatory RNA, proteomics) emerged in order to identify biomarkers for early diagnosis and prognosis of complex diseases and therefore facilitating the development of novel treatment approaches...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29784843/high-dose-and-delayed-treatment-with-bile-acids-ineffective-in-rml-prion-infected-mice
#11
Grant Norman, Jody Campeau, Valerie L Sim
Prion diseases are a group of neurodegenerative diseases associated with the misfolding of the cellular prion protein (PrPC ) into the infectious form (PrPSc ). There are currently no treatments for prion disease. Bile acids have the ability to protect hepatocytes from apoptosis and are neuroprotective in animal models of other protein folding neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Importantly, bile acids are approved for clinical use in patients with cirrhosis, and have recently been shown to be safe and possibly effective in pilot trials of patients with amyotrophic lateral sclerosis (ALS)...
May 21, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29783990/severe-hepatopathy-and-neurological-deterioration-after-start-of-valproate-treatment-in-a-6-year-old-child-with-mitochondrial-tryptophanyl-trna-synthetase-deficiency
#12
Elise Vantroys, Joél Smet, Arnaud V Vanlander, Sarah Vergult, Ruth De Bruyne, Frank Roels, Hedwig Stepman, Herbert Roeyers, Björn Menten, Rudy Van Coster
BACKGROUND: The first subjects with deficiency of mitochondrial tryptophanyl-tRNA synthetase (WARS2) were reported in 2017. Their clinical characteristics can be subdivided into three phenotypes (neonatal phenotype, severe infantile onset phenotype, Parkinson-like phenotype). RESULTS: Here, we report on a subject who presented with early developmental delay, motor weakness and intellectual disability and who was considered during several years as having a non-progressive encephalopathy...
May 21, 2018: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/29783690/echinacoside-an-inestimable-natural-product-in-treatment-of-neurological-and-other-disorders
#13
REVIEW
Jingjing Liu, Lingling Yang, Yanhong Dong, Bo Zhang, Xueqin Ma
Echinacoside (ECH), a natural phenylethanoid glycoside, was first isolated from Echinacea angustifolia DC. (Compositae) sixty years ago. It was found to possess numerous pharmacologically beneficial activities for human health, especially the neuroprotective and cardiovascular effects. Although ECH showed promising potential for treatment of Parkinson's and Alzheimer's diseases, some important issues arose. These included the identification of active metabolites as having poor bioavailability in prototype form, the definite molecular signal pathways or targets of ECH with the above effects, and limited reliable clinical trials...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29783643/hydroxysafflor-yellow-a-attenuates-lipopolysaccharide-induced-neurotoxicity-and-neuroinflammation-in-primary-mesencephalic-cultures
#14
Tian Wang, Yu-Xin Ding, Jie He, Cheng-Jun Ma, Yue Zhao, Zhen-Hua Wang, Bing Han
Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson's disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius . The purpose of this study was to investigate whether HSYA could attenuate LPS-induced neurotoxicity and neuroinflammation in primary mesencephalic cultures. Cell viability was measured by MTT and LDH assays...
May 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29782440/management-for-simultaneous-patella-tendon-and-anterior-cruciate-ligament-ruptures-a-systematic-review-of-available-literature
#15
Alexander Handel Matthews, Ethan James Fraser, Benjamin Parkinson
BACKGROUND: Combined rupture of the anterior cruciate ligament (ACL) and patella tendon (PT) is a rare injury pattern. Currently little evidence exists to help guide management decisions for these patients. METHODS: A systematic literature search was conducted using PubMed (MEDLINE) and Scopus (EMBASE, MEDLINE) for all articles reporting on combined rupture of the anterior cruciate ligament (ACL) and patella tendon (PT). The characteristic injury mechanisms, common presentation findings and outcomes of simultaneous and staged treatment strategies were determined to provide guidance for the management of this uncommon injury pattern...
May 15, 2018: Journal of Orthopaedic Trauma
https://www.readbyqxmd.com/read/29781786/sitagliptin-rescues-memory-deficits-in-parkinsonian-rats-via-upregulating-bdnf-to-prevent-neuron-and-dendritic-spine-loss
#16
Jing Li, Shuhu Zhang, Chenye Li, Mei Li, Lan Ma
OBJECTIVES: Parkinson's disease (PD) is a neurodegenerative disease with high morbidity among adults worldwide that causes tremendous trouble to people's lives. The purpose of this study was to investigate the impact of sitagliptin on PD and its potential mechanism. METHODS: First, the memory of rats in each group was evaluated with the Morris water maze (MWM) test and the passive avoidance test. Then, both brain-derived neurotrophic factor (BDNF) protein and mRNA levels were detected by ELISA and qPCR assays, respectively...
May 21, 2018: Neurological Research
https://www.readbyqxmd.com/read/29780852/parkinson-s-patients-with-dyskinesia-switched-from-immediate-release-amantadine-to-open-label-ads-5102
#17
Stuart H Isaacson, Stanley Fahn, Rajesh Pahwa, Caroline M Tanner, Alberto J Espay, Claudia Trenkwalder, Charles H Adler, Rajiv Patni, Reed Johnson
Background: ADS-5102 (amantadine) extended release capsules (GOCOVRI™) are a treatment for dyskinesia in patients with Parkinson's disease (PD). ADS-5102 reduced dyskinesia and OFF time in phase 3 controlled trials of up to six months. Amantadine immediate release (IR) is used for dyskinesia, but suboptimal durability and tolerability limit its clinical utility. Methods: In an ongoing, open-label, phase 3 study in the US and Western Europe (NCT02202551), patients with PD received 274 mg of ADS-5102 (equivalent to 340 mg amantadine HCl) once daily at bedtime for up to two years...
March 2018: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/29780333/neurological-soft-signs-spontaneous-and-treatment-emergent-extrapyramidal-syndromes-in-black-africans-with-first-episode-schizophrenia
#18
Akin Ojagbemi, Bonga Chiliza, Toyin Bello, Laila Asmal, Oluyomi Esan, Robin Emsley, Oye Gureje
Background: Very little is known about the relationship between spontaneous and treatment-induced motor syndromes in Africans with first episode schizophrenia. Objective: We investigated the association between spontaneous NSS and EPS, with treatment-induced EPS in a homogenous sample of Black Africans with first episode schizophrenia. Methods: We examined Xhosa (South Africa) and Yoruba (Nigeria) patients, using the Neurological Evaluation Scale and extrapyramidal symptoms scale before and at 3 months after exposure to low dose flupenthixol decanoate...
2018: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/29779963/action-potential-initiation-propagation-and-cortical-invasion-in-the-hyperdirect-pathway-during-subthalamic-deep-brain-stimulation
#19
Ross W Anderson, AmirAli Farokhniaee, Kabilar Gunalan, Bryan Howell, Cameron C McIntyre
BACKGROUND: High frequency (∼130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. However, numerous questions remain to be addressed on the basic biophysics of hyperdirect pathway stimulation...
May 12, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29779721/evaluation-of-an-ontology-based-system-for-computerized-cognitive-rehabilitation
#20
Anna Alloni, Silvana Quaglini, Silvia Panzarasa, Elena Sinforiani, Sara Bernini
OBJECTIVES: This paper describes the results of a randomized clinical trial about the effectiveness of a computerized rehabilitation treatment on a sample of 31 patients affected by Parkinson disease. METHODS: Computerized exercises were administered by the therapists to the intervention group (n = 17) through the CoRe tool, which automatically generates a big variety of exercises leveraging on a stimuli set (words, sounds and images) organized into a dedicated ontology...
July 2018: International Journal of Medical Informatics
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