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Parkinson‘s disease

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https://www.readbyqxmd.com/read/30342766/chchd2-mutational-screening-in-brazilian-patients-with-familial-parkinson-s-disease
#1
Danielle D Voigt, Caroline M Nascimento, Ritiele B de Souza, Pedro H Cabello Acero, Mário Campos Júnior, Camilla P da Silva, João S Pereira, Ana Lucia Rosso, Marco A Araujo Leite, Luiz Felipe R Vasconcellos, Marcus V Della Coletta, Delson J da Silva, Denise H Nicaretta, Andressa P Gonçalves, Jussara M Dos Santos, Veluma Calassara, Cíntia B Santos-Rebouças, Márcia M G Pimentel
Robust evidence on the involvement of genetic factors in the etiology of Parkinson's disease (PD) expands our knowledge about monogenic causes that contribute for this important neurodegenerative disorder. Mutations in the CHCHD2 gene have been linked to autosomal dominant forms of PD, although there is still lack of evidence for CHCHD2 variants leading to the disease in mixed populations as those from South America. To assess the contribution of CHCHD2 as a causal factor for familial PD in Brazil, one of the most heterogeneous populations in the world, we conducted the first molecular analysis of the CHCHD2 gene in a cohort of 122 index cases from Brazilian families with autosomal dominant forms of PD...
September 27, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30342392/widespread-diffusion-changes-differentiate-parkinson-s-disease-and-progressive-supranuclear-palsy
#2
Aron S Talai, Jan Sedlacik, Kai Boelmans, Nils D Forkert
BACKGROUND: Parkinson's disease (PD) and progressive supranuclear palsy - Richardson's syndrome (PSP-RS) are often represented by similar clinical symptoms, which may challenge diagnostic accuracy. The objective of this study was to investigate and compare regional cerebral diffusion properties in PD and PSP-RS subjects and evaluate the use of these metrics for an automatic classification framework. MATERIAL AND METHODS: Diffusion-tensor MRI datasets from 52 PD and 21 PSP-RS subjects were employed for this study...
October 4, 2018: NeuroImage: Clinical
https://www.readbyqxmd.com/read/30342073/visual-detection-of-affordances-for-aperture-negotiation-in-people-with-parkinson-disease
#3
Ben Sidaway, Aimee Aaroe, D Monique Albert, Kristen Brasier, Garrett Desrosiers, Megan Keith, Alexandra Laniewski, Jaime Knowles, Caryce Morell, Jason Prada, Jessica Stuart, Rachel Voicechovski
BACKGROUND: An essential requirement for the guidance of action in cluttered environments is that people can accurately perceive what actions are afforded by particular surroundings given the person's action capabilities. Research has shown that healthy young individuals turn their shoulders when walking through a doorway when the aperture is less than a certain percentage of their shoulder width and that they are able to detect this critical width with visual inspection. These findings imply that movements are constrained by perception of the environment in body-scaled units...
October 17, 2018: Neuropsychologia
https://www.readbyqxmd.com/read/30341316/hsp90-incorporating-chaperome-networks-as-biosensor-for-disease-related-pathways-in-patient-specific-midbrain-dopamine-neurons
#4
Sarah Kishinevsky, Tai Wang, Anna Rodina, Sun Young Chung, Chao Xu, John Philip, Tony Taldone, Suhasini Joshi, Mary L Alpaugh, Alexander Bolaender, Simon Gutbier, Davinder Sandhu, Faranak Fattahi, Bastian Zimmer, Smit K Shah, Elizabeth Chang, Carmen Inda, John Koren, Nathalie G Saurat, Marcel Leist, Steven S Gross, Venkatraman E Seshan, Christine Klein, Mark J Tomishima, Hediye Erdjument-Bromage, Thomas A Neubert, Ronald C Henrickson, Gabriela Chiosis, Lorenz Studer
Environmental and genetic risk factors contribute to Parkinson's Disease (PD) pathogenesis and the associated midbrain dopamine (mDA) neuron loss. Here, we identify early PD pathogenic events by developing methodology that utilizes recent innovations in human pluripotent stem cells (hPSC) and chemical sensors of HSP90-incorporating chaperome networks. We show that events triggered by PD-related genetic or toxic stimuli alter the neuronal proteome, thereby altering the stress-specific chaperome networks, which produce changes detected by chemical sensors...
October 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/30338296/early-onset-parkinson-disease-caused-by-a-mutation-in-chchd2-and-mitochondrial-dysfunction
#5
Richard G Lee, Maryam Sedghi, Mehri Salari, Anne-Marie J Shearwood, Maike Stentenbach, Ariana Kariminejad, Hayley Goullee, Oliver Rackham, Nigel G Laing, Homa Tajsharghi, Aleksandra Filipovska
Objective: Our goal was to identify the gene(s) associated with an early-onset form of Parkinson disease (PD) and the molecular defects associated with this mutation. Methods: We combined whole-exome sequencing and functional genomics to identify the genes associated with early-onset PD. We used fluorescence microscopy, cell, and mitochondrial biology measurements to identify the molecular defects resulting from the identified mutation. Results: Here, we report an association of a homozygous variant in CHCHD2 , encoding coiled-coil-helix-coiled-coil-helix domain containing protein 2, a mitochondrial protein of unknown function, with an early-onset form of PD in a 26-year-old Caucasian woman...
October 2018: Neurology. Genetics
https://www.readbyqxmd.com/read/30337193/evaluation-of-novel-parkinson-s-disease-candidate-genes-in-the-chinese-population
#6
Elaine Guo Yan Chew, Herty Liany, Louis C S Tan, Wing-Lok Au, Kumar-M Prakash, Azlina Ahmad Annuar, Anne Y Y Chan, Shen-Yang Lim, Vincent Mok, Sun Ju Chung, Kyuyoung Song, Jianjun Liu, Jia Nee Foo, Eng-King Tan
Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples...
September 21, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/30336354/monoamine-oxidase-a-promotes-protective-autophagy-in-human-sh-sy5y-neuroblastoma-cells-through-bcl-2-phosphorylation
#7
Aslihan Ugun-Klusek, Theodosis S Theodosi, Julia C Fitzgerald, Florence Burté, Christoph Ufer, David J Boocock, Patrick Yu-Wai-Man, Lynn Bedford, E Ellen Billett
Monoamine oxidases (MAOs) are located on the outer mitochondrial membrane and are drug targets for the treatment of neurological disorders. MAOs control the levels of neurotransmitters in the brain via oxidative deamination and contribute to reactive oxygen species (ROS) generation through their catalytic by-product H2 O2 . Increased ROS levels may modulate mitochondrial function and mitochondrial dysfunction is implicated in a vast array of disorders. However, the downstream effects of MAO-A mediated ROS production in a neuronal model has not been previously investigated...
October 9, 2018: Redox Biology
https://www.readbyqxmd.com/read/30334640/rotenone-impairs-oxidant-antioxidant-balance-both-in-brain-and-intestines-in-zebrafish
#8
İsmail Ünal, Ünsal V Üstündağ, Perihan S Ateş, Gizem Eğilmezer, Ahmet A Alturfan, Türkan Yiğitbaşı, Ebru Emekli-Alturfan
Rotenone is a commonly used pesticide that inhibits complex I of the mitochondrial electron transport system. Rotenone exposed rats demonstrate many characteristics of Parkinson Disease (PD). Oxidative stress is one of the hallmarks of PD, being the major sources of ROS in the DA neurons. In recent years the strong connection between the intestinal environment and the function of the central nervous system (CNS) has gained widespread popularity. In order to explain the mechanism underlying the GI dysfunction in PD, we aimed to investigate oxidant-antioxidant status in the brain and intestine, as well as locomotor activity, in rotenone exposed zebrafish...
October 18, 2018: International Journal of Neuroscience
https://www.readbyqxmd.com/read/30327480/author-correction-computer-keyboard-interaction-as-an-indicator-of-early-parkinson-s-disease
#9
L Giancardo, A Sánchez-Ferro, T Arroyo-Gallego, I Butterworth, C S Mendoza, P Montero, M Matarazzo, J A Obeso, M L Gray, R San José Estépar
A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.
October 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30327218/impact-of-small-vessel-disease-on-severity-of-motor-and-cognitive-impairment-in-parkinson-s-disease
#10
Raymond S Schwartz, Glenda M Halliday, Derrick Soh, Dennis J Cordato, Jillian J Kril
BACKGROUND: Subcortical small vessel disease and vascular risk factors are associated with motor and cognitive impairment. In this study we examined the relationship between these factors and the severity of motor impairment and dementia in pathologically-confirmed Parkinson's disease (PD). METHODS: The extent and severity of small vessel disease (SVD) was assessed pathologically in 77 patients with PD. The severity of motor impairment was determined using a cumulative index derived from longitudinal measures of Hoehn and Yahr score...
October 13, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/30326945/abi3-and-plcg2-missense-variants-as-risk-factors-for-neurodegenerative-diseases-in-caucasians-and-african-americans
#11
Olivia J Conway, Minerva M Carrasquillo, Xue Wang, Jenny M Bredenberg, Joseph S Reddy, Samantha L Strickland, Curtis S Younkin, Jeremy D Burgess, Mariet Allen, Sarah J Lincoln, Thuy Nguyen, Kimberly G Malphrus, Alexandra I Soto, Ronald L Walton, Bradley F Boeve, Ronald C Petersen, John A Lucas, Tanis J Ferman, William P Cheshire, Jay A van Gerpen, Ryan J Uitti, Zbigniew K Wszolek, Owen A Ross, Dennis W Dickson, Neill R Graff-Radford, Nilüfer Ertekin-Taner
BACKGROUND: Rare coding variants ABI3_rs616338-T and PLCG2_rs72824905-G were identified as risk or protective factors, respectively, for Alzheimer's disease (AD). METHODS: We tested the association of these variants with five neurodegenerative diseases in Caucasian case-control cohorts: 2742 AD, 231 progressive supranuclear palsy (PSP), 838 Parkinson's disease (PD), 306 dementia with Lewy bodies (DLB) and 150 multiple system atrophy (MSA) vs. 3351 controls; and in an African-American AD case-control cohort (181 AD, 331 controls)...
October 11, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/30326851/retrospective-assessment-of-patient-characteristics-and-healthcare-costs-prior-to-a-diagnosis-of-alzheimer-s-disease-in-an-administrative-claims-database
#12
Radhika Nair, Virginia S Haynes, Mir Siadaty, Nick C Patel, Adam S Fleisher, Derek Van Amerongen, Michael M Witte, AnnCatherine M Downing, Leslie Ann Hazel Fernandez, Vishal Saundankar, Daniel E Ball
BACKGROUND: The objective of this study was to examine patient characteristics and health care resource utilization (HCRU) in the 36 months prior to a confirmatory diagnosis of Alzheimer's disease (AD) compared to a matched cohort without dementia during the same time interval. METHODS: Patients newly diagnosed with AD (with ≥2 claims) were identified between January 1, 2013 to September 31, 2015, and the date of the second claim for AD was defined as the index date...
October 16, 2018: BMC Geriatrics
https://www.readbyqxmd.com/read/30322477/pet-imaging-in-movement-disorders
#13
REVIEW
Baijayanta Maiti, Joel S Perlmutter
Positron emission tomography (PET) has revealed key insights into the pathophysiology of movement disorders. This paper will focus on how PET investigations of pathophysiology are particularly relevant to Parkinson disease, a neurodegenerative condition usually starting later in life marked by a varying combination of motor and nonmotor deficits. Various molecular imaging modalities help to determine what changes in brain herald the onset of pathology; can these changes be used to identify presymptomatic individuals who may be appropriate for to-be-developed treatments that may forestall onset of symptoms or slow disease progression; can PET act as a biomarker of disease progression; can molecular imaging help enrich homogenous cohorts for clinical studies; and what other pathophysiologic mechanisms relate to nonmotor manifestations...
November 2018: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/30321664/iron-quantification-in-parkinson-s-disease-using-an-age-based-threshold-on-susceptibility-maps-the-advantage-of-local-versus-entire-structure-iron-content-measurements
#14
Sean K Sethi, Shawn J Kisch, Kiarash Ghassaban, Ali Rajput, Alex Rajput, Paul S Babyn, Saifeng Liu, Peter Szkup, E Mark Haacke
BACKGROUND: Elevated brain iron has been observed in Idiopathic Parkinson's disease (IPD) within the deep gray matter. Using quantitative susceptibility mapping (QSM) and a thresholded high-iron region, we quantified iron content in the midbrain of patients with Parkinson's disease as a function of age. METHODS: We used MRI to scan 24 IPD patients at 3-Tesla. Susceptibility-weighted images were collected with the following parameters, TE: 6 and 20 ms, TR: 30 ms, FA: 15°, and resolution: 0...
October 13, 2018: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/30320583/an-inducible-alpha-synuclein-expressing-neuronal-cell-line-model-for-parkinson-s-disease1
#15
Velmarini Vasquez, Joy Mitra, George Perry, K S Rao, Muralidhar L Hegde
Altered expression of α-synuclein is linked to Parkinson's disease (PD). A major challenge to explore how the increased α-synuclein affect neurotoxicity is the lack of a suitable human neuronal cell model that mimics this scenario. Its expression in neural precursors affects their differentiation process, in addition to the neuronal adaptability and variability in maintaining a constant level of expression across passages. Here, we describe an SH-SY5Y line harboring Tet-ON SNCA cDNA cassette that allows for induction of controlled α-synuclein expression after neuronal differentiation, which can be an important tool for PD research...
September 29, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/30319772/east-indian-sandalwood-santalum-album-l-oil-confers-neuroprotection-and-geroprotection-in-caenorhabditis-elegans-via-activating-skn-1-nrf2-signaling-pathway
#16
A Mohankumar, G Shanmugam, D Kalaiselvi, C Levenson, S Nivitha, G Thiruppathi, P Sundararaj
East Indian Sandalwood Oil (EISO) has diverse beneficial effects and has been used for thousands of years in traditional folk-medicine for treatment of different human ailments. However, there has been no in-depth scientific investigation to decipher the neuroprotective and geroprotective mechanism of EISO and its principle components, α- and β-santalol. Hence the current study was undertaken to assess the protective effects of EISO, and α- and β-santalol against neurotoxic (6-OHDA/6-hydroxydopamine) and proteotoxic (α-synuclein) stresses in a Caenorhabditis elegans model...
October 3, 2018: RSC Advances
https://www.readbyqxmd.com/read/30319343/parameters-of-surface-electromyogram-suggest-that-dry-immersion-relieves-motor-symptoms-in-patients-with-parkinsonism
#17
German G Miroshnichenko, Alexander Yu Meigal, Irina V Saenko, Liudmila I Gerasimova-Meigal, Liudmila A Chernikova, Natalia S Subbotina, Saara M Rissanen, Pasi A Karjalainen
Dry immersion (DI) is acknowledged as a reliable space flight analog condition. At DI, subject is immersed in water being wrapped in a waterproof film to imitate microgravity (μG). Microgravity is known to decrease muscle tone due to deprivation of the sensory stimuli that activate the reflexes that keep up the muscle tone. In contrary, parkinsonian patients are characterized by elevated muscle tone, or rigidity, along with rest tremor and akinesia. We hypothesized that DI can diminish the elevated muscle tone and/or the tremor in parkinsonian patients...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/30316070/snca-variants-and-alpha-synuclein-level-in-cd45-blood-cells-in-parkinson-s-disease
#18
A Emelyanov, D Kulabukhova, L Garaeva, K Senkevich, E Verbitskaya, M Nikolaev, P Andoskin, A Kopytova, I Milyukhina, A Yakimovskii, A Timofeeva, L Prakhova, A Ilves, I Vlasova, S Pchelina
Parkinson's disease (PD) is the second most frequent neurodegenerative disorder. Impaired metabolism of alpha-synuclein (SNCA) and its aggregation are implicated in PD pathogenesis. SNCA has been identified as a highly significant genetic risk loci associated with the sporadic form of PD in across populations in GWAS and replicative studies. In this study we conducted a genetic analysis of five SNCA single nucleotide polymorphisms (SNPs) (rs356219, rs2619364, rs11931074, rs2583988, rs356168) in 458 PD patients and 353 from North-West region of Russia...
October 3, 2018: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/30309226/cerebral-small-vessel-disease-a-review-focusing-on-pathophysiology-biomarkers-and-machine-learning-strategies
#19
Elisa Cuadrado-Godia, Pratistha Dwivedi, Sanjiv Sharma, Angel Ois Santiago, Jaume Roquer Gonzalez, Mercedes Balcells, John Laird, Monika Turk, Harman S Suri, Andrew Nicolaides, Luca Saba, Narendra N Khanna, Jasjit S Suri
Cerebral small vessel disease (cSVD) has a crucial role in lacunar stroke and brain hemorrhages and is a leading cause of cognitive decline and functional loss in elderly patients. Based on underlying pathophysiology, cSVD can be subdivided into amyloidal and non-amyloidal subtypes. Genetic factors of cSVD play a pivotal role in terms of unraveling molecular mechanism. An important pathophysiological mechanism of cSVD is blood-brain barrier leakage and endothelium dysfunction which gives a clue in identification of the disease through circulating biological markers...
September 2018: Journal of Stroke
https://www.readbyqxmd.com/read/30303934/two-year-agility-maintenance-training-slows-the-progression-of-parkinsonian-symptoms
#20
József Tollár, Ferenc Nagy, Norbert Kovács, Tibor Hortobágyi
INTRODUCTION: Parkinson's disease (PD) is a progressive neurodegenerative condition and it is unclear if long-term non-pharmaceutical interventions can slow the progression of motor and non-motor symptoms and lower drug dose. METHODS: In a randomized trial, after an initial 3-week-long, 15-session supervised high-intensity sensorimotor agility exercise (E) program designed to improve postural instability, the Exercise+Maintenance (E+M, n=19) group continued to exercise three times per week for 2 years, while E (n=16) and the no exercise and no maintenance control (C, n=20) continued habitual living...
October 9, 2018: Medicine and Science in Sports and Exercise
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