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https://www.readbyqxmd.com/read/29342421/the-relation-between-plasma-%C3%AE-synuclein-level-and-clinical-symptoms-or-signs-of-parkinson-s-disease
#1
Michalina Malec-Litwinowicz, Andrzej Plewka, Danuta Plewka, Edyta Bogunia, Michał Morek, Andrzej Szczudlik, Michał Szubiga, Monika Rudzińska-Bar
INTRODUCTION: Parkinson disease (PD) is the common neurodegenerative disease. α-Synuclein (ASN), main aggregating protein in neural cells of CNS in PD, was found in peripheral fluids. Testing ASN in plasma is potential test for diagnose PD, but previous studies are controversial. The aim of this study was to investigate if plasma ASN level may be a valuable biomarker, is the level of plasma ASN concentration different in various motor subtypes of diseases, is there a relation between the level of plasma ASN and the severity of motor symptoms...
November 21, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/29342318/optical-structural-analysis-of-individual-%C3%AE-synuclein-oligomers
#2
Juan Alberto Varela, Margarida Rodrigues, Suman De, Patrick Flagmeier, Sonia Gandhi, Christopher M Dobson, David Klenerman, Steven Lee
Small aggregates of misfolded proteins play a key role in neurodegenerative disorders. Such species are difficult to study due to the lack of methods capable of resolving these heterogeneous aggregates, which are smaller than the optical diffraction limit. We demonstrate here an all-optical fluorescence microscopy method to characterise the structure of individual protein-aggregates based on the fluorescence anisotropy of dyes such as thioflavin-T, and show that this technology is capable of studying oligomers in human biofluids such as cerebrospinal fluid...
January 17, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29341898/induction-of-alpha-synuclein-pathology-in-the-enteric-nervous-system-of-the-rat-and-non-human-primate-results-in-gastrointestinal-dysmotility-and-transient-cns-pathology
#3
Fredric P Manfredsson, Kelvin C Luk, Matthew J Benskey, Aysegul Guezer, Joanna Garcia, Nathan C Kuhn, Ivette M Sandoval, Joseph R Patterson, Alana O'Mara, Reid Yonkers, Jeffrey H Kordower
Alpha-Synuclein (α-syn) is by far the most highly vetted pathogenic and therapeutic target in Parkinson's disease. Aggregated α-syn is present in sporadic Parkinson's disease, both in the central nervous system (CNS) and peripheral nervous system (PNS). The enteric division of the PNS is of particular interest because 1) gastric dysfunction is a key clinical manifestation of Parkinson's disease, and 2) Lewy pathology in myenteric and submucosal neurons of the enteric nervous system (ENS) has been referred to as stage zero in the Braak pathological staging of Parkinson's disease...
January 13, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29341798/phenolic-constituents-and-inhibitory-effects-of-hibiscus-sabdariffa-l-sorrel-calyx-on-cholinergic-monoaminergic-and-purinergic-enzyme-activities
#4
Ganiyu Oboh, Taiwo M Adewuni, Adedayo O Ademiluyi, Tosin A Olasehinde, Ayokunle O Ademosun
This study revealed the effect of phenolic extract from Hibiscus sabdariffa L. (sorrel) calyx on acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase (MAO), and ecto-5' nucleotidase (E-NTDase) activities as well as pro-oxidant-induced oxidative damage in rat brain in vitro. Sorrel extract inhibited AChE (EC50 = 46.96 µg/mL), BChE (EC50 = 40.38 µg/mL), MAO (EC50 = 43.69 µg/mL), and E-NTDase (EC50 = 40.52 µg/mL) and stimulated Na+/K+-ATPase (EC50 = 22.01 µg/mL) activities. The phenolic extract also reduced Fe2+- (EC50 = 22...
January 17, 2018: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/29341412/3d-neuromelanin-sensitive-magnetic-resonance-imaging-of-the-substantia-nigra-in-parkinson-s-disease
#5
Shweta Prasad, Albert Stezin, Abhishek Lenka, Lija George, Jitender Saini, Ravi Yadav, Pramod Kumar Pal
BACKGROUND: To investigate the diagnostic utility of signal intensity measurement of the substantia nigra pars compacta (SNc) using three dimensional (3D) neuromelanin-sensitive 31MRI, for discrimination of patients with PD from healthy controls. METHODS: T1-weighted neuromelanin sensitive images of 16 patients with PD and 15 controls were quantitatively analyzed by placing circular 10mm2 regions of interest (ROI) over the central and lateral parts of bilateral SNc, and anterior to the cerebral aqueduct at 3 levels of the midbrain...
January 17, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#6
REVIEW
Jianhua Zhang, M Lillian Culp, Jason G Craver, Victor Darley-Usmar
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis...
January 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29340951/a-perspective-on-multi-target-drug-discovery-and-design-for-complex-diseases
#7
Rona R Ramsay, Marija R Popovic-Nikolic, Katarina Nikolic, Elisa Uliassi, Maria Laura Bolognesi
Diseases of infection, of neurodegeneration (such as Alzheimer's and Parkinson's diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets...
January 17, 2018: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/29340928/microbiota-signaling-pathways-that-influence-neurologic-disease
#8
REVIEW
Laura M Cox, Howard L Weiner
Though seemingly distinct and autonomous, emerging evidence suggests there is a bidirectional interaction between the intestinal microbiota and the brain. This crosstalk may play a substantial role in neurologic diseases, including anxiety, depression, autism, multiple sclerosis, Parkinson's disease, and, potentially, Alzheimer's disease. Long hypothesized by Metchnikoff and others well over 100 years ago, investigations into the mind-microbe axis is now seeing a rapid resurgence of research. If specific pathways and mechanisms of interaction are understood, it could have broad therapeutic potential, as the microbiome is environmentally acquired and can be modified to promote health...
January 16, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29340614/association-of-polygenic-risk-score-with-cognitive-decline-and-motor-progression-in-parkinson-disease
#9
Kimberly C Paul, Jessica Schulz, Jeff M Bronstein, Christina M Lill, Beate R Ritz
Importance: Genetic factors have a well-known influence on Parkinson disease (PD) susceptibility. The largest genome-wide association study (GWAS) identified 26 independent single-nucleotide polymorphisms (SNPs) associated with PD risk. Among patients, the course and severity of symptom progression is variable, and little is known about the potential association of genetic factors with phenotypic variance. Objective: To assess whether GWAS-identified PD risk SNPs also have a cumulative association with the progression of cognitive and motor symptoms in patients with PD...
January 16, 2018: JAMA Neurology
https://www.readbyqxmd.com/read/29340288/7t-mri-subthalamic-nucleus-atlas-for-use-with-3t-mri
#10
Mikhail Milchenko, Scott A Norris, Kathleen Poston, Meghan C Campbell, Mwiza Ushe, Joel S Perlmutter, Abraham Z Snyder
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces motor symptoms in most patients with Parkinson disease (PD), yet may produce untoward effects. Investigation of DBS effects requires accurate localization of the STN, which can be difficult to identify on magnetic resonance images collected with clinically available 3T scanners. The goal of this study is to develop a high-quality STN atlas that can be applied to standard 3T images. We created a high-definition STN atlas derived from seven older participants imaged at 7T...
January 2018: Journal of Medical Imaging
https://www.readbyqxmd.com/read/29339826/using-intracellular-markers-to-identify-a-novel-set-of-surface-markers-for-live-cell-purification-from-a-heterogeneous-hipsc-culture
#11
Elizabeth J Paik, Alison L O'Neil, Shi-Yan Ng, Chicheng Sun, Lee L Rubin
Human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) can provide sources for midbrain dopaminergic (mDA) neural progenitors (NPCs) for cell therapy to treat Parkinson's disease (PD) patients. However, the well-known line-to-cell line variability in the differentiation capacity of individual cell lines needs to be improved for the success of this therapy. To address this issue, we sought to identify mDA NPC specific cell surface markers for fluorescence activated cell sorting (FACS). Through RNA isolation after sorting for NPCs based on staining for cell-specific transcription factors followed by microarray, we identified two positive cell surface markers (CORIN and CD166) and one negative cell surface marker (CXCR4) for mDA NPC sorting...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339765/mutations-in-bassoon-in-individuals-with-familial-and-sporadic-progressive-supranuclear-palsy-like-syndrome
#12
Ichiro Yabe, Hiroaki Yaguchi, Yasutaka Kato, Yasuo Miki, Hidehisa Takahashi, Satoshi Tanikawa, Shinichi Shirai, Ikuko Takahashi, Mari Kimura, Yuka Hama, Masaaki Matsushima, Shinsuke Fujioka, Takahiro Kano, Masashi Watanabe, Shin Nakagawa, Yasuyuki Kunieda, Yoshio Ikeda, Masato Hasegawa, Hiroshi Nishihara, Toshihisa Ohtsuka, Shinya Tanaka, Yoshio Tsuboi, Shigetsugu Hatakeyama, Koichi Wakabayashi, Hidenao Sasaki
Clinical diagnosis of progressive supranuclear palsy (PSP) is sometimes difficult because various phenotypes have been identified. Here, we report a mutation in the bassoon (BSN) gene in a family with PSP-like syndrome. Their clinical features resembled not only those of PSP patients but also those of individuals with multiple system atrophy and Alzheimer's disease. The neuropathological findings showed a novel three + four repeat tauopathy with pallido-luysio-nigral degeneration and hippocampal sclerosis...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339638/a-nomogram-to-characterize-the-severity-of-detrusor-overactivity-during-the-ice-water-test-description-of-the-method-and-proof-of-concept
#13
André Reitz, Tanja Hüsch, Axel Haferkamp
AIMS: To develop a nomogram with severity categories for detrusor overactivity (DO). METHODS: By conducting ice water tests (IWT) in 55 patients with Parkinson's disease, we identified criteria to describe characteristics of the detrusor pressure curves: (1) a gradient of Δpdet over Δt at the maximum detrusor pressure and (2) the area under the curve. In a nomogram, 10 severity categories of DO were established: 1 and 2 were assigned to group A (mild), 3 and 4 to group B (moderate) and 5-10 to group C (severe)...
January 16, 2018: Urologia Internationalis
https://www.readbyqxmd.com/read/29339630/comparison-of-the-efficacy-of-different-drugs-on-non-motor-symptoms-of-parkinson-s-disease-a-network-meta-analysis
#14
Bao-Dong Li, Jing-Jun Cui, Jia Song, Ce Qi, Pei-Feng Ma, Ya-Rong Wang, Jing Bai
BACKGROUND/AIMS: A network meta-analysis is used to compare the efficacy of ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil and levodopa, with placebo as a control, for non-motor symptoms in Parkinson's disease (PD). METHODS: PubMed, Embase and the Cochrane Library were searched from their establishment dates up to January 2017 for randomized controlled trials (RCTs) investigating the efficacy of the above ten drugs on the non-motor symptoms of PD...
January 15, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29339319/treatment-with-the-noradrenaline-re-uptake-inhibitor-atomoxetine-alone-and-in-combination-with-the-%C3%AE-2-adrenoceptor-antagonist-idazoxan-attenuates-loss-of-dopamine-and-associated-motor-deficits-in-the-lps-inflammatory-rat-model-of-parkinson-s-disease
#15
Justin D Yssel, Eoin O'Neill, Yvonne M Nolan, Thomas J Connor, Andrew Harkin
The impact of treatment with the noradrenaline (NA) re-uptake inhibitor atomoxetine and the α2-adrenoceptor (AR) antagonist idazoxan in an animal model of Parkinson's disease (PD) was assessed. Concurrent systemic treatment with atomoxetine and idazoxan, a combination which serves to enhance the extra-synaptic availability of NA, exerts anti-inflammatory and neuroprotective effects following delivery of an inflammatory stimulus, the bacterial endotoxin, lipopolysaccharide (LPS) into the substantia nigra. Lesion-induced deficits in motor function (akinesia, forelimb-use asymmetry) and striatal dopamine (DA) loss were rescued to varying degrees depending on the treatment...
January 12, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29339253/design-synthesis-and-bioevalucation-of-novel-2-3-dihydro-1h-inden-1-amine-derivatives-as-potent-and-selective-human-monoamine-oxidase-b-inhibitors-based-on-rasagiline
#16
Xuan Xiao, Xing-Xing Zhang, Mei-Miao Zhan, Kai Cheng, Shiyu Li, Zhouling Xie, Chenzhong Liao
Parkinson's disease (PD) is associated with elevated levels of hMAO-B in the brain, and MAO-B has been recognized a successful target for developing anti-PD drugs. Herein we report rasagiline derivatives as novel potent and selective hMAO-B inhibitors. They were designed by employing fragment-based drug design strategy to link rasagiline and hydrophobic fragments, which may target a hydrophobic pocket in the entrance cavity of hMAO-B. Different linkers such as -OCH2-, -SCH2-, -OCH2CH2-, -OCH2CH2O-, -OCH2CH2CH2O- were tried...
January 10, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29339106/safinamide-a-new-hope-for-parkinson-s-disease
#17
REVIEW
Fábio G Teixeira, Miguel F Gago, Paulo Marques, Pedro Silva Moreira, Ricardo Magalhães, Nuno Sousa, António J Salgado
The loss of dopaminergic neurons (DAn) and reduced dopamine (DA) production underlies the reasoning behind the gold standard treatment for Parkinson's disease (PD) using levodopa (L-DOPA). Recently licensed by the European Medicine Agency (EMA) and US Food and Drug Administration (FDA), safinamide [a monoamine oxidase B (MOA-B) inhibitor] is an alternative to L-DOPA; as we discuss here, it enhances dopaminergic transmission with decreased secondary effects compared with L-DOPA. In addition, nondopaminergic actions (neuroprotective effects) have been reported, with safinamide inhibiting glutamate release and sodium/calcium channels, reducing the excitotoxic input to dopaminergic neuronal death...
January 12, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29339103/comparative-review-of-adult-midbrain-and-striatum-neurogenesis-with-classical-neurogenesis
#18
REVIEW
Parisa Farzanehfar
Parkinson's Disease (PD) motor symptoms are caused by loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) of the midbrain. Dopamine cell replacement therapy (DA CRT), either by cell transplantation or endogenous repair, has been a potential treatment to replace dead cells and improve PD motor symptoms. Adult midbrain and striatum have been studied for many years to find evidence of neurogenesis. Although the literature is controversial, recent research has revived the possibility of neurogenesis here...
January 12, 2018: Neuroscience Research
https://www.readbyqxmd.com/read/29339052/neurophysiological-effects-in-cortico-basal-ganglia-thalamic-circuits-of-antidyskinetic-treatment-with-5-ht1a-receptor-biased-agonists
#19
Ivani Brys, Pär Halje, Robson Scheffer-Teixeira, Mark Varney, Adrian Newman-Tancredi, Per Petersson
Recently, the biased and highly selective 5-HT1A agonists, NLX-112, F13714 and F15599, have been shown to alleviate dyskinesia in rodent and primate models of Parkinson's disease, while marginally interfering with antiparkinsonian effects of levodopa. To provide more detailed information on the processes underlying the alleviation of dyskinesia, we have here investigated changes in the spectral contents of local field potentials in cortico-basal ganglia-thalamic circuits following treatment with this novel group of 5-HT1A agonists or the prototypical agonist, 8-OH-DPAT...
January 12, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29338936/continuous-intestinal-infusion-of-levodopa-carbidopa-in-patients-with-advanced-parkinson-s-disease-in-spain-subanalysis-by-autonomous-community
#20
D Santos-García, M J Catalán, V Puente, F Valldeoriola, I Regidor, P Mir, J Matías-Arbelo, J C Parra, F Grandas
OBJECTIVES: To compare the characteristics of patients undergoing treatment with continuous intestinal infusion of levodopa-carbidopa (CIILC) for advanced Parkinson's disease and the data on the effectiveness and safety of CIILC in the different autonomous communities (AC) of Spain. METHODS: A retrospective, longitudinal, observational study was carried out into 177 patients from 11 CAs who underwent CIILC between January 2006 and December 2011. We analysed data on patients' clinical and demographic characteristics, variables related to effectiveness (changes in off time/on time with or without disabling dyskinesia; changes in Hoehn and Yahr scale and Unified Parkinson's Disease Rating Scale scores; non-motor symptoms; and Clinical Global Impression scale scores) and safety (adverse events), and the rate of CIILC discontinuation...
January 12, 2018: Neurología: Publicación Oficial de la Sociedad Española de Neurología
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