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https://www.readbyqxmd.com/read/28107736/crystal-structures-binding-interactions-and-adme-evaluation-of-brain-penetrant-n-substituted-indazole-5-carboxamides-as-subnanomolar-selective-monoamine-oxidase-b-and-dual-mao-a-b-inhibitors
#1
Nikolay T Tzvetkov, Hans-Georg Stammler, Beate Neumann, Silvia Hristova, Liudmil Antonov, Marcus Gastreich
The pharmacological and physicochemical analysis of structurally optimized N-alkyl-substituted indazole-5-carboxamides, developed as potential drug and radioligand candidates for the treatment and diagnosis of Parkinson's disease (PD) and other neurological disorders, is reported. Recent efforts have been focused on the development of subnanomolar potent, selective MAO-B (N1-alkyl-substituted compounds 12a-14a and 15) and dual active MAO-A/B (N2-methylated compounds 12b-14b) inhibitors with nanomolar potency towards MAO-B and moderately active against MAO-A enzyme, respectively...
January 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28107119/olfaction-new-understandings-diagnostic-applications
#2
Gabrielle F Ruggiero, Jeannette Y Wick
Estimates indicate that 14 million Americans have olfactory dysfunction. As with other senses, such as sight and hearing, olfaction frequently declines with age. Impaired olfaction can be a warning sign of Parkinson's disease, sometimes occurring before motor symptoms develop. It's also an initial symptom of Alzheimer's dementia (AD); the amyloid plaques and tangles characterizing AD invade the olfactory bulb and hippocampus early in its course, hampering odor identification. Olfactory dysfunction is associated with some serious problems, including inability to smell warning odors (fire, gas) and impaired ability to taste food...
November 1, 2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
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
#3
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/28106571/the-identification-of-alpha-synuclein-as%C3%A2-the%C3%A2-first-parkinson-disease-gene
#4
Robert L Nussbaum
No abstract text is available yet for this article.
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106570/replacing-dopamine-neurons-in%C3%A2-parkinson-s-disease-how-did-it-happen
#5
Anders Björklund, Olle Lindvall
No abstract text is available yet for this article.
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106569/cerebellar-volume-and-executive-function-in-parkinson-disease-with-and-without-freezing-of-gait
#6
Peter S Myers, Marie E McNeely, Jonathan M Koller, Gammon M Earhart, Meghan C Campbell
BACKGROUND: Freezing of gait (FOG) affects approximately 50% of people with Parkinson Disease (PD), impacting quality of life and placing financial and emotional strain on the individual and caregivers. People with PD and FOG have similar deficits in motor adaptation and cognition as individuals with cerebellar lesions, indicating the cerebellum may play a role in FOG. OBJECTIVE: To examine potential differences in cerebellar volumes and their relationships with cognition between PD with (FOG+) and without FOG (FOG-)...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106568/physical-therapy-versus-a-general-exercise-programme-in-patients-with-hoehn-yahr-stage-ii-parkinson-s-disease-a%C3%A2-randomized-controlled-trial
#7
Savina Dipasquale, Roberto Meroni, Francesco Sasanelli, Ivan Messineo, Daniele Piscitelli, Cecilia Perin, Cesare Maria Cornaggia, Cesare G Cerri
BACKGROUND AND OBJECTIVE: Several studies suggest that general exercise (GE) and physical therapy programmes (PT) improve the outcomes of Parkinson's disease (PD) patients; however, the available data do not allow a determination of which treatment is more effective. Our study aims to compare the effects of physiotherapy and general exercise in Parkinson's disease. METHODS: Design and setting: Randomized controlled trial -general hospital outpatient clinic. The participants were patients with Hoehn Yahr stage II PD...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106567/fractional-anisotropy-and-mean-diffusion-as-measures-of-dopaminergic-function-in-parkinson-s-disease-challenging-results
#8
Niklas Lenfeldt, Johan Eriksson, Björn Åström, Lars Forsgren, Susanna Jakobson
BACKGROUND: Diffusion tensor imaging (DTI) has been purported as an imaging technique to assess dopaminergic degeneration in Parkinson's disease. OBJECTIVE: To test if fractional anisotropy (FA) and mean diffusion (MD) in the basal ganglia as measured by DTI correlates with dopaminergic function as measured by dopamine transporter (DAT) and dopamine D2-receptor (D2R) SPECT. METHODS: One-hundred and eleven patients with Parkinson's disease (71±10 years) and thirty-one controls (68±7 years) performed DTI, DAT and D2R SPECT at baseline and four follow-ups (1-year: 89 patients/zero controls; 3-year: 72/11; 5-year: 48/17; and 8-year: 13/13)...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106566/cerebral-amyloid-burden-and-hoehn-and-yahr-stage-3-scoring-in-parkinson-disease
#9
Vikas Kotagal, Nicolaas I Bohnen, Martijn L T M Müller, Kirk A Frey, Roger L Albin
BACKGROUND: Progression to Hoehn and Yahr (HY) stage 3 marks the transition to advanced disease staging and disability in Parkinson disease (PD). OBJECTIVE/METHODS: We conducted a case-control study of 36 PD subjects at HY stage 2.5 or 3, with groups matched for gender, age, and disease duration. Positron Emission tomography (PET) imaging included dihydrotetrabenazine [11C]DTBZ and Pittsburgh Compound B [11C]PiB. RESULTS: Subjects with HY 2...
January 17, 2017: Journal of Parkinson's Disease
https://www.readbyqxmd.com/read/28106473/overexpression-of-buffy-enhances-the-loss-of-parkin-and-suppresses-the-loss-of-pink1-phenotypes-in-drosophila
#10
P Githure M'Angale, Brian E Staveley
Mutations in parkin (PARK2) and Pink1 (PARK6) are responsible for autosomal recessive forms of early onset Parkinson's disease (PD). Attributed to the failure of neurons to clear dysfunctional mitochondria, loss of gene expression leads to loss of nigrostriatal neurons. The Pink1/parkin pathway plays a role in the quality control mechanism aimed at eliminating defective mitochondria, and the failure of this mechanism results in a reduced lifespan and impaired locomotor ability, among other phenotypes. Inhibition of parkin or Pink1 through the induction of stable RNAi transgene in the Ddc-Gal4-expressing neurons results in such phenotypes to model PD...
December 22, 2016: Genome Génome / Conseil National de Recherches Canada
https://www.readbyqxmd.com/read/28106099/nesfatin-1-protects-dopaminergic-neurons-against-mpp-mptp-induced-neurotoxicity-through-the-c-raf-erk1-2-dependent-anti-apoptotic-pathway
#11
Xiao-Li Shen, Ning Song, Xi-Xun Du, Yong Li, Jun-Xia Xie, Hong Jiang
Several brain-gut peptides have been reported to have a close relationship with the central dopaminergic system; one such brain-gut peptide is nesfatin-1. Nesfatin-1 is a satiety peptide that is predominantly secreted by X/A-like endocrine cells in the gastric glands, where ghrelin is also secreted. We previously reported that ghrelin exerted neuroprotective effects on nigral dopaminergic neurons, which implied a role for ghrelin in Parkinson's disease (PD). In the present study, we aim to clarify whether nesfatin-1 has similar effects on dopaminergic neurons both in vivo and in vitro...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28106066/the-psychosis-spectrum-in-parkinson-disease
#12
REVIEW
Dominic H Ffytche, Byron Creese, Marios Politis, K Ray Chaudhuri, Daniel Weintraub, Clive Ballard, Dag Aarsland
In 2007, the clinical and research profile of illusions, hallucinations, delusions and related symptoms in Parkinson disease (PD) was raised with the publication of a consensus definition of PD psychosis. Symptoms that were previously deemed benign and clinically insignificant were incorporated into a continuum of severity, leading to the rapid expansion of literature focusing on clinical aspects, mechanisms and treatment. Here, we review this literature and the evolving view of PD psychosis. Key topics include the prospective risk of dementia in individuals with PD psychosis, and the causal and modifying effects of PD medication...
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28106064/precision-medicine-for-disease-modification-in-parkinson-disease
#13
REVIEW
Alberto J Espay, Patrik Brundin, Anthony E Lang
No abstract text is available yet for this article.
January 20, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28106025/aneurysm-of-the-muscular-septum-associated-with-wolf-parkinson-white-syndrome-presenting-as-dilated-cardiomyopathy-a-report-of-two-cases
#14
Vehbi Doğan, İlker Ertuğrul, Şeyma Kayalı, Utku Arman Örün, Selmin Karademir
Muscular septal aneurysms are extremely rare without a ventricular septal defect and are diagnosed accidentally in most cases. Reported cases generally have rhythm disturbance or electrocardiographic findings of Wolf-Parkinson-White (WPW) syndrome. Presently described are 2 cases of ventricular septal aneurysm associated with WPW syndrome, which presented as dilated cardiomyopathy. Pre-excitation disappeared gradually in first patient. There was also concurrent decrease in degree of bulging of the interventricular septum and improvement of left ventricular systolic function...
January 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28105978/simultaneous-transplantation-of-fetal-ventral-mesencephalic-tissue-and-encapsulated-genetically-modified-cells-releasing-gdnf-in-a-hemi-parkinsonian-rat-model-of-parkinson-s-disease
#15
Alberto Perez-Bouza, Stefano Di, Stefanie Seiler, Morten Meyer, Lukas Andereggen, Alexander Huber, Raphael Guzman, Hans R
Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor or mocktransfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior and 2, 4, 6 and 9 weeks post-transplantation...
January 20, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28105729/whole-genome-grey-and-white-matter-dna-methylation-profiles-in-dorsolateral-prefrontal-cortex
#16
Jose Vicente Sanchez-Mut, Holger Heyn, Enrique Vidal, Raúl Delgado-Morales, Sebastian Moran, Sergi Sayols, Juan Sandoval, Isidre Ferrer, Manel Esteller, Johannes Gräff
The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood...
January 20, 2017: Synapse
https://www.readbyqxmd.com/read/28105503/using-swallow-tail-sign-and-putaminal-hypointensity-as-biomarkers-to-distinguish-multiple-system-atrophy-from-idiopathic-parkinson-s-disease-a-susceptibility-weighted-imaging-study
#17
Na Wang, HuaGuang Yang, ChengBo Li, GuoGuang Fan, XiaoGuang Luo
OBJECTIVE: To investigate the value of 'swallow-tail' sign and putaminal hypointensity on 3 T susceptibility-weighted imaging (SWI) for distinguishing multiple system atrophy (MSA) from idiopathic Parkinson's disease (IPD). METHODS: Three groups - 39 MSA patients, 18 IPD patients,and 31 healthy controls (HCs) - were administered a 3 T SWI sequence to evaluate 'swallow-tail' sign and putaminal hypointensity using visual scales from 0 to 2 and 0 to 3 scores, respectively...
January 19, 2017: European Radiology
https://www.readbyqxmd.com/read/28105331/opioid-system-in-l-dopa-induced-dyskinesia
#18
REVIEW
Jing Pan, Huaibin Cai
L-3, 4-Dihydroxyphenylalanine (L-DOPA)-induced dyskinesia (LID) is a major clinical complication in the treatment of Parkinson's disease (PD). This debilitating side effect likely reflects aberrant compensatory responses for a combination of dopaminergic neuron denervation and repeated L-DOPA administration. Abnormal endogenous opioid signal transduction pathways in basal ganglia have been well documented in LID. Opioid receptors have been targeted to alleviate the dyskinesia. However, the exact role of this altered opioid activity is remains under active investigation...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28104909/selective-neuronal-vulnerability-in-parkinson-disease
#19
D James Surmeier, José A Obeso, Glenda M Halliday
Intracellular α-synuclein (α-syn)-rich protein aggregates called Lewy pathology (LP) and neuronal death are commonly found in the brains of patients with clinical Parkinson disease (cPD). It is widely believed that LP appears early in the disease and spreads in synaptically coupled brain networks, driving neuronal dysfunction and death. However, post-mortem analysis of human brains and connectome-mapping studies show that the pattern of LP in cPD is not consistent with this simple model, arguing that, if LP propagates in cPD, it must be gated by cell- or region-autonomous mechanisms...
January 20, 2017: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/28104397/pink1-alleviates-myocardial-hypoxia-reoxygenation-injury-by-ameliorating-mitochondrial-dysfunction
#20
Yang Li, Liangxian Qiu, Xiping Liu, Zhiwen Hou, Bo Yu
PTEN inducible kinase-1 (PINK1) mutant induces mitochondrial dysfunction of cells, resulting in an inherited form of Parkinson's disease. However its exact role in the cardiomyocytes is unclear. The present study examined the function of PINK1 in hypoxia-reoxygenation (H/R) induced H9c2 cell damage and its potential mechanism. The H/R model in H9c2 cells was established by 6 h of hypoxia and 12 h of reoxygenation. The CCK8 and LDH assay indicated that the cell viability was obviously reduced after H/R. The expression of PINK1 was decreased in H/R-induced H9c2 cells compared with control group...
January 16, 2017: Biochemical and Biophysical Research Communications
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