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https://www.readbyqxmd.com/read/29792872/association-of-glucocerebrosidase-polymorphisms-and-mutations-with-dementia-in-incident-parkinson-s-disease
#1
Kristin Aaser Lunde, Janete Chung, Ingvild Dalen, Kenn Freddy Pedersen, Jan Linder, Magdalena E Domellöf, Eva Elgh, Angus D Macleod, Charalampos Tzoulis, Jan Petter Larsen, Ole-Bjørn Tysnes, Lars Forsgren, Carl E Counsell, Guido Alves, Jodi Maple-Grødem
INTRODUCTION: Both polymorphisms and mutations in glucocerebrosidase (GBA) may influence the development of dementia in patients with Parkinson's disease. METHODS: Four hundred forty-two patients and 419 controls were followed for 7 years. Dementia was diagnosed using established criteria. Participants were analyzed for GBA genetic variants, including E326K, T369M, and L444P. Associations between GBA carrier status and dementia were assessed with Cox survival analysis...
May 21, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29792848/subthalamic-nucleus-deep-brain-stimulation-protects-neurons-by-activating-autophagy-via-pp2a-inactivation-in-a-rat-model-of-parkinson-s-disease
#2
Ting-Ting Du, Ying-Chuan Chen, Yong-Quan Lu, Fan-Gang Meng, Hui Yang, Jian-Guo Zhang
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapeutic strategy for alleviating disability in patients with moderate to severe Parkinson's disease (PD). Preclinical studies have shown that stimulation of the rat STN can protect against nigral dopaminergic neuron loss. However, the underlying mechanism is unclear. To investigate the molecular basis of the neuroprotective effects of STN stimulation, a rat model of PD was established by unilaterally injecting 6-hydroxydopamine (6-OHDA) into the striatum...
May 21, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29792714/docking-screens-for-dual-inhibitors-of-disparate-drug-targets-for-parkinson-s-disease
#3
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/29792572/galnac-sirna-conjugates-leading-the-way-for-delivery-of-rnai-therapeutics
#4
Aaron D Springer, Steven F Dowdy
Short-interfering RNA (siRNA)-induced RNAi responses have great potential to treat a wide variety of human diseases from cancer to pandemic viral outbreaks to Parkinson's Disease. However, before siRNAs can become drugs, they must overcome a billion years of evolutionary defenses designed to keep invading RNAs on the outside cells from getting to the inside of cells. Not surprisingly, significant effort has been placed in developing a wide array of delivery technologies. Foremost of these has been the development of N-acetylgalactosamine (GalNAc) siRNA conjugates for delivery to liver...
May 24, 2018: Nucleic Acid Therapeutics
https://www.readbyqxmd.com/read/29791914/atlas-independent-electrophysiological-mapping-of-the-optimal-locus-of-subthalamic-deep-brain-stimulation-for-the-motor-symptoms-of-parkinson-disease
#5
Erin C Conrad, James M Mossner, Kelvin L Chou, Parag G Patil
BACKGROUND/AIMS: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor symptoms of Parkinson disease (PD). However, motor outcomes can be variable, perhaps due to inconsistent positioning of the active contact relative to an unknown optimal locus of stimulation. Here, we determine the optimal locus of STN stimulation in a geometrically unconstrained, mathematically precise, and atlas-independent manner, using Unified Parkinson Disease Rating Scale (UPDRS) motor outcomes and an electrophysiological neuronal stimulation model...
May 23, 2018: Stereotactic and Functional Neurosurgery
https://www.readbyqxmd.com/read/29791783/in-silico-and-wet-bench-interactomics-sheds-light-on-the-similitudes-and-differences-between-human-roco-proteins
#6
Jean-Marc Taymans, Marie-Christine Chartier-Harlin
Defining a common and specific functions for homologs of a novel protein family is not a trivial task. In their recent study, Tomkins and colleagues have addressed this challenge for the ROCO protein family by exploring interactomes of its four human members: MASL1, DAPK1, LRRK1 and LRRK2. ROCO proteins are characterized by a Ras-GTPase domain embedded in complex multidomain proteins and a functional descriptor for this protein family has been elusive despite accumulating research, particularly for LRRK2, a protein implicated in Parkinson's disease...
May 23, 2018: Proteomics
https://www.readbyqxmd.com/read/29791652/inflammatory-myopathy-in-the-context-of-an-unusual-overlapping-laminopathy
#7
Cristina Guillín-Amarelle, Sofía Sánchez-Iglesias, Antonio Mera, Elena Pintos, Ana Castro-Pais, Leticia Rodríguez-Cañete, Julio Pardo, Felipe F Casanueva, David Araújo-Vilar
Laminopathies are genetic disorders associated with alterations in nuclear envelope proteins, known as lamins. The LMNA gene encodes lamins A and C, and LMNA mutations have been linked to diseases involving fat (type 2 familial partial lipodystrophy [FPLD2]), muscle (type 2 Emery-Dreifuss muscular dystrophy [EDMD2], type 1B limb-girdle muscular dystrophy [LGMD1B], and dilated cardiomyopathy), nerves (type 2B1 Charcot-Marie-Tooth disease), and premature aging syndromes. Moreover, overlapping syndromes have been reported...
May 17, 2018: Archives of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29791244/the-need-for-mapping-personal-goals-to-exercise-dosage-in-community-based-exercise-programs-for-people-with-parkinson-s-disease
#8
Allison L Amateis, Chelsea L Boesel, Bryan P Ehnert, Abby S Evans, Katheryn E Hurst, Katie L Marek, Amanda C Sullivan, Kathryn R Zalewski, Wendy E Huddleston
PURPOSE: Community-based exercise can support long-term management of Parkinson's disease, although it is not known if personal goals are met in these programs. The objectives of this study were to: (1) examine the goals of community based exercise programs from the participant and instructor perspectives; (2) establish the extent to which these programs meet self-described exercise outcomes; and (3) explore participant and instructor perspectives on barriers to meeting exercise expectations...
May 23, 2018: Physiotherapy Theory and Practice
https://www.readbyqxmd.com/read/29790977/alpha-synuclein-aggregates-in-labial-salivary-glands-of-idiopathic-rapid-eye-movement-sleep-behavior-disorder
#9
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/29790571/-epidemiology-of-alzheimer-s-disease-and-other-dementias
#10
REVIEW
J Garre-Olmo
INTRODUCTION: Dementia is a clinical syndrome resulting from a number of causations and which is usually accompanied by progressive and diffuse brain dysfunction. The different subtypes are characterised by a clinical picture with common symptoms that differ in terms of their aetiology, age, clinical presentation, clinical course and associated disorders. AIM: To present an update on the information available about the descriptive epidemiology of dementia and its main subtypes...
June 1, 2018: Revista de Neurologia
https://www.readbyqxmd.com/read/29790195/a-licence-to-drive-neurological-illness-loss-and-disruption
#11
Melissa Stepney, Susan Kirkpatrick, Louise Locock, Suman Prinjha, Sara Ryan
The sense of freedom and independence that being able to drive generates may be taken for granted by many until it is threatened by illness. Drawing on the 'mobility turn' in social sciences that emphasises the social and emotional significance of the car (Sheller and Urry , ), this article presents secondary analysis of narratives of driving and its significance across four neurological conditions (epilepsy, Parkinson's disease, transient ischaemic attack and motor neurone disease). Taking an interactionist approach we explore how the withdrawal of a driving licence can represent not just a practical and emotional loss of independence, but also loss of enjoyment; of a sense and feeling of 'normal' adulthood and social participation; and of an identity (in some cases gendered) of strength and power...
May 22, 2018: Sociology of Health & Illness
https://www.readbyqxmd.com/read/29789389/lrrk2-is-a-negative-regulator-of-mycobacterium-tuberculosis-phagosome-maturation-in-macrophages
#12
Anetta Härtlova, Susanne Herbst, Julien Peltier, Angela Rodgers, Orsolya Bilkei-Gorzo, Antony Fearns, Brian D Dill, Heyne Lee, Rowan Flynn, Sally A Cowley, Paul Davies, Patrick A Lewis, Ian G Ganley, Jennifer Martinez, Dario R Alessi, Alastair D Reith, Matthias Trost, Maximiliano G Gutierrez
Mutations in the leucine-rich repeat kinase 2 (LRRK2) are associated with Parkinson's disease, chronic inflammation and mycobacterial infections. Although there is evidence supporting the idea that LRRK2 has an immune function, the cellular function of this kinase is still largely unknown. By using genetic, pharmacological and proteomics approaches, we show that LRRK2 kinase activity negatively regulates phagosome maturation via the recruitment of the Class III phosphatidylinositol-3 kinase complex and Rubicon to the phagosome in macrophages...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29789378/subthalamic-nucleus-neurons-differentially-encode-early-and-late-aspects-of-speech-production
#13
W J Lipski, A Alhourani, T Pirnia, P W Jones, C Dastolfo-Hromack, L B Helou, D J Crammond, S Shaiman, M W Dickey, L L Holt, R S Turner, J A Fiez, R M Richardson
Basal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery in humans with Parkinson's disease, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in sync with motor execution aspects of speech. Nearly half of seventy-nine unit recordings exhibited firing rate modulation, during a syllable reading task across twelve subjects (male and female)...
May 22, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29789205/genetic-variants-related-to-urate-and-risk-of-parkinson-s-disease
#14
Katherine C Hughes, Xiang Gao, Eilis J O'Reilly, Iris Y Kim, Molin Wang, Marc G Weisskopf, Michael A Schwarzschild, Alberto Ascherio
INTRODUCTION: Higher urate concentrations have been associated with a lower risk of developing Parkinson's disease (PD) and with slower rates of clinical decline in PD patients. Whether these associations reflect a neuroprotective effect of urate is unclear. Our objective was to assess whether genetic variants that modify circulating urate levels are also associated with altered PD risk. METHODS: Participants were from three large ongoing cohort studies: the Nurses' Health Study (NHS), the Health Professionals Follow-up Study (HPFS), and the Cancer Prevention Study II Nutrition Cohort (CPS-IIN)...
May 1, 2018: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29788997/2d-versus-3d-human-induced-pluripotent-stem-cell-derived-cultures-for-neurodegenerative-disease-modelling
#15
REVIEW
Eduarda G Z Centeno, Helena Cimarosti, Angela Bithell
Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS), affect millions of people every year and so far, there are no therapeutic cures available. Even though animal and histological models have been of great aid in understanding disease mechanisms and identifying possible therapeutic strategies, in order to find disease-modifying solutions there is still a critical need for systems that can provide more predictive and physiologically relevant results...
May 22, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29788869/advances-in-the-tyrosinase-inhibitors-from-plant-source
#16
Marco Bonesi, Jianbo Xiao, Rosa Tundis, Francesca Aiello, Vincenzo Sicari, Monica R Loizzo
Tyrosinase is a multifunctional copper-containing oxidase which catalyses the oxidation of tyrosine to produce melanin. The alteration in melanin biosynthesis occurs in many diseases. The pigment has a protecting role against skin photo-carcinogenesis, but anomalous melanin pigmentation is an aesthetic problem in human beings. Moreover, the formation of neuromelanin in human brain could contribute to the neurodegeneration associated with Parkinson's disease. Finally, tyrosinase is also responsible of undesired browning in fruits and vegetables...
May 21, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29788783/a-mixed-methods-approach-to-understanding-the-palliative-needs-of-parkinson-s-patients
#17
Lindsay P Prizer, Jennifer L Gay, Mark G Wilson, Kerstin G Emerson, Anne P Glass, Janis M Miyasaki, Molly M Perkins
Parkinson's disease (PD) is the second-most common age-related neurodegenerative disorder. Despite recommendations for a palliative approach, little is known about what palliative needs are unmet by standard care. This study aims to (a) identify palliative needs of PD patients, (b) determine the relationship between palliative needs and health-related quality of life (HRQoL), and (c) probe into factors affecting HRQoL. PD patients and neurologists were recruited for a survey on palliative need; a subset of patients was interviewed...
May 1, 2018: Journal of Applied Gerontology: the Official Journal of the Southern Gerontological Society
https://www.readbyqxmd.com/read/29788069/inflammatory-bowel-disease-and-parkinson-s-disease-a-nationwide-swedish-cohort-study
#18
Petra Weimers, Jonas Halfvarson, Michael C Sachs, Rachel Saunders-Pullman, Jonas F Ludvigsson, Inga Peter, Johan Burisch, Ola Olén
Background: Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD). Methods: To estimate the incidence and relative risk of PD development in a cohort of adult IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis [UC]: n = 24,422; Crohn's disease [CD]: n = 11,418; IBD-unclassified [IBD-U]: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520)...
May 16, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29787739/apathy-in-individuals-with-parkinson-s-disease-associated-with-mild-cognitive-impairment-a-neuropsychological-investigation
#19
Alberto Costa, Antonella Peppe, Silvia Zabberoni, Francesco Scalici, Carlo Caltagirone, Giovanni Augusto Carlesimo
Apathy is frequently reported in individuals with Parkinson's disease (PD) and is hypothesized to be associated with frontal-striatal related cognitive functions. Available data, however, do not provide univocal results. Moreover, this relationship has been poorly investigated in PD patients with mild cognitive impairment (MCI). This study was aimed at investigating the association between severity of apathy of PD patients and their performance on neuropsychological tests investigating executive abilities. Individuals with PD (i...
May 19, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/29787640/elevated-levels-of-8-ohdg-and-park7-dj-1-in-peri-implantitis-mucosa
#20
Gökhan Kasnak, Erhan Firatli, Eija Könönen, Vakur Olgac, Fares Zeidán-Chuliá, Ulvi Kahraman Gursoy
BACKGROUND: Reactive oxygen species contribute to periodontal tissue homeostasis under control of anti-oxidative responses. Disruption in this balance induces severe inflammation and extended tissue degradation. PURPOSE: Aim of this study was to identify the expression levels of nuclear factor, erythroid 2 like 2 (NFE2L2/NRF2), Parkinsonism associated deglycase (PARK7/DJ-1), kelch-like ECH associated protein 1 (KEAP1), and 8-hydroxy-deoxyguanosine (8-OHdG) in peri-implant mucosal tissues affected by peri-implantitis, and to compare the levels to those of periodontally diseased and healthy tissue samples...
May 22, 2018: Clinical Implant Dentistry and related Research
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