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https://www.readbyqxmd.com/read/28829427/recombinant-%C3%AE-%C3%AE-and-%C3%AE-synucleins-stimulate-protein-phosphatase-2a-catalytic-subunit-activity-in-cell-free-assays
#1
Sovanarak Lek, Javier Vargas-Medrano, Ernesto Villanueva, Brian Marcus, Wesley Godfrey, Ruth G Perez
α-Synuclein (aSyn), β-Synuclein (bSyn), and γ-Synuclein (gSyn) are members of a conserved family of chaperone-like proteins that are highly expressed in vertebrate neuronal tissues. Of the three synucleins, only aSyn has been strongly implicated in neurodegenerative disorders such as Parkinson's disease, Dementia with Lewy Bodies, and Multiple System Atrophy. In studying normal aSyn function, data indicate that aSyn stimulates the activity of the catalytic subunit of an abundantly expressed dephosphorylating enzyme, PP2Ac in vitro and in vivo...
August 13, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28828924/use-of-ancillary-tests-when-determining-brain-death-in-pediatric-patients-in-the-united-states
#2
Ariane Lewis, Nellie Adams, Arun Chopra, Matthew P Kirschen
Although pediatric brain death guidelines stipulate when ancillary testing should be used during brain death determination, little is known about the way these recommendations are implemented in clinical practice. We conducted a survey of pediatric intensivists and neurologists in the United States on the use of ancillary testing. Although most respondents noted they only performed an ancillary test if the clinical examination and apnea test could not be completed, 20% of 195 respondents performed an ancillary test for other reasons, including (1) to convince a family that objected to the brain death determination that a patient is truly dead (n=21), (2) personal preference (n=14), and (3) institutional requirement (n=5)...
January 1, 2017: Journal of Child Neurology
https://www.readbyqxmd.com/read/28828740/the-oligomer-hypothesis-in-%C3%AE-synucleinopathy
#3
REVIEW
Kenjiro Ono
Lewy bodies and Lewy neurites in the brain constitute the main histopathological features of Parkinson's disease (PD) and dementia with Lewy bodies. They comprise amyloid-like fibrils composed of α-synuclein (αS), a small protein (~14 kDa). Because the aggregation of αS in the brain has been implicated as a critical step in the development of these diseases, the research for disease-modifying drugs has focused on modification of the αS aggregation process in the brain. Recent studies using synthetic αS peptides, a cell culture model, transgenic mice models, and human samples such as cerebrospinal fluids and the blood of PD patients have suggested that pre-fibrillar forms of αS (i...
August 21, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28827325/targeted-pet-imaging-strategy-to-differentiate-malignant-from-inflamed-lymph-nodes-in-diffuse-large-b-cell-lymphoma
#4
Jun Tang, Darin Salloum, Brandon Carney, Christian Brand, Susanne Kossatz, Ahmad Sadique, Jason S Lewis, Wolfgang A Weber, Hans-Guido Wendel, Thomas Reiner
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma in adults. DLBCL exhibits highly aggressive and systemic progression into multiple tissues in patients, particularly in lymph nodes. Whole-body (18)F-fluodeoxyglucose positron emission tomography ([(18)F]FDG-PET) imaging has an essential role in diagnosing DLBCL in the clinic; however, [(18)F]FDG-PET often faces difficulty in differentiating malignant tissues from certain nonmalignant tissues with high glucose uptake. We have developed a PET imaging strategy for DLBCL that targets poly[ADP ribose] polymerase 1 (PARP1), the expression of which has been found to be much higher in DLBCL than in healthy tissues...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28826526/small-molecule-pet-tracers-for-imaging-proteinopathies
#5
REVIEW
Chester A Mathis, Brian J Lopresti, Milos D Ikonomovic, William E Klunk
In this chapter, we provide a review of the challenges and advances in developing successful PET imaging agents for 3 major types of aggregated amyloid proteins: amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These 3 amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer disease, Lewy body dementias, multiple system atrophy, and frontotemporal dementias, among others. In the Introduction section, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts...
September 2017: Seminars in Nuclear Medicine
https://www.readbyqxmd.com/read/28820063/loss-in-toxic-function-of-aggregates-of-%C3%AE-synuclein-mutants-by-a-%C3%AE-synuclein-derived-peptide
#6
Soheila Mohammadi, Maryam Nikkhah, Saman Hosseinkhani
Parkinson's disease (PD) primarily results from a severe and selective damage of dopaminergic neurons. The neuropathological hallmark of the disease is the presence of inclusions known as Lewy bodies, that are enriched in α-Synuclein (αS) nanofibrils, within the surviving neurons. The inhibition of αS aggregation is considered as an efficient approach for preventing or treating PD. To date, several researchers have been focused on screening for the inhibitors that are able to block, slow down, or reverse αS aggregation, particularly at its early stages...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28815699/application-of-the-condensed-protocol-for-the-nia-aa-guidelines-for-the-neuropathologic-assessment-of-alzheimer-s-disease-in-an-academic-clinical-practice
#7
Rajnish Bharadwaj, Patrick J Cimino, Margaret E Flanagan, Caitlin S Latimer, Luis F Gonzalez-Cuyar, Gordana Juric-Sekhar, Thomas J Montine, Desiree A Marshall, C Dirk Keene
AIMS: In response to concerns regarding resource expenditures required to fully implement the 2012 NIA-AA Sponsored Guidelines for the neuropathologic assessment of Alzheimer's disease (AD), we previously developed a sensitive and cost-reducing Condensed Protocol (CP) at the University of Washington (UW) Alzheimer's Disease Research Center (ADRC) that consolidated the recommended NIA-AA protocol into fewer cassettes requiring fewer immunohistochemical stains. The CP was not designed to replace NIA-AA protocols, but instead to make the NIA-AA criteria accessible to clinical and forensic neuropathology practices where resources limit full implementation of NIA-AA guidelines...
August 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28811697/role-of-iron-and-copper-in-the-pathogenesis-of-parkinson-s-disease
#8
Mohit Kumar Gangania, Jyoti Batra, Suman Kushwaha, Rachna Agarwal
Parkinson's disease (PD) is an old age disorder of basal ganglia which involves oligomerization of α-synuclein protein and formation of intercellular inclusions known as "Lewy bodies" in substantia nigra and caudate nuclei in brain which is progressive in nature. It is second most prevalent neurodegenerative disorder characterized by tremor at rest, muscle rigidity, slowness of movement (bradykinesia, akinesia), and changes in posture (instability). Both excess and deficiency in levels of transition metals (especially iron, copper) can be detrimental to the central nervous system...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28811268/antecedent-adhd-dementia-and-metabolic-dysregulation-a-u-s-based-cohort-analysis
#9
Keith Fluegge, Kyle Fluegge
INTRODUCTION: Epidemiological and genetic studies have reported a link between antecedent ADHD and dementia. The underpinning mechanisms of these associations are not known and have generated considerable speculation. METHODS: We have extracted hospitalization discharge data on dementia and ADHD (representing a severe phenotype) from the Healthcare Cost and Utilization Project (HCUPnet) and utilized a Poisson regression with two-ways fixed effects to investigate this association...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28808912/molecular-imaging-and-updated-diagnostic-criteria-in-lewy-body-dementias
#10
REVIEW
Nicolaas I Bohnen, Martijn L T M Müller, Kirk A Frey
PURPOSE OF REVIEW: The aims of the study were to review recent advances in molecular imaging in the Lewy body dementias (LBD) and determine if these may support the clinical but contested temporal profile distinction between Parkinson disease (PD) with dementia (PDD) versus dementia with Lewy bodies (DLB). RECENT FINDINGS: There do not appear to be major regional cerebral metabolic or neurotransmitter distinctions between PDD and DLB. However, recent studies highlight the relative discriminating roles of Alzheimer proteinopathies...
August 14, 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28808780/non-cns-pathogenic-origin-of-parkinson-s-disease
#11
Humdoon Choudhry, Lawrence C Perlmuter
The gut with its variety of microbiota may serve as an etiological origin of diseases. Gut microbes may also play a role in the pathogenesis of diseases beyond their simple nutritional maintenance and support. For example, gut protein aggregation, possibly aided by microbes as well as nasal influences, might be linked to disease that may move to the brain through the vagus nerve. To this end, Braak has offered a "dual-hit" hypothesis that proposes a novel etiology for Parkinson's disease (PD). The hypothesis places the initial origin of the disease in the nose and the gastrointestinal tract (GI) after infection by an unknown pathogen that could aggregate in the gut and then eventually spread to the brain via the autonomic plexuses...
August 14, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28806386/aripiprazole-improves-psychotic-cognitive-and-motor-symptoms-in-a-patient-with-lewy-body-dementia
#12
Cho Lee, Yu-Chih Shen
No abstract text is available yet for this article.
August 10, 2017: Journal of Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28805588/weight-in-parkinson-s-disease-phenotypical-significance
#13
Jagdish C Sharma, Anna Lewis
Body weight in Parkinson's disease (PD) is a significant nonmotor feature. Weight homeostasis is a complex physiological process and gets deranged in PD patients leading to changes in weight. While both the low and high body weight have been reported as risk factors for PD, the majority of PD patients have a lower weight and a subset of patients lose weight during the course of the disease, while a small proportion gain weight. A number of clinical parameters such as older age, impaired cognition, severity of disease, and an imbalance of food intake determined by satiety and hunger hormones have been reported to be associated with but not the cause of weight change...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28804999/diversity-of-astroglial-responses-across-human-neurodegenerative-disorders-and-brain-aging
#14
Isidro Ferrer
Astrogliopathy refers to alterations of astrocytes occurring in diseases of the nervous system, and it implies the involvement of astrocytes as key elements in the pathogenesis and pathology of diseases and injuries of the central nervous system. Reactive astrocytosis refers to the response of astrocytes to different insults to the nervous system, whereas astrocytopathy indicates hypertrophy, atrophy/degeneration and loss of function and pathological remodeling occurring as a primary cause of a disease or as a factor contributing to the development and progression of a particular disease...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28801960/mri-characterization-of-brown-adipose-tissue-under-thermal-challenges-in-normal-weight-overweight-and-obese-young-men
#15
Jie Deng, Lisa M Neff, Nicholas C Rubert, Bin Zhang, Richard M Shore, Jonathan D Samet, Paige C Nelson, Lewis Landsberg
PURPOSE: To implement quantitative Dixon magnetic resonance imaging (MRI) methods for brown adipose tissue (BAT) characterization at inactive and cold-activated states in normal weight, overweight, and obese subjects. The hypotheses are that MRI characteristics of BAT would differentiate between nonobese and obese subjects, and activation of BAT in response to thermal challenges that are detected by MRI would be correlated with BAT activity measured by positron emission tomography / computed tomography (PET/CT)...
August 11, 2017: Journal of Magnetic Resonance Imaging: JMRI
https://www.readbyqxmd.com/read/28801743/investigation-of-an-optimal-cell-lysis-method-for-the-study-of-the-zinc-metalloproteome-of-histoplasma-capsulatum
#16
Anna M Donnell, Stephanie Lewis, Sami Abraham, Kavitha Subramanian, Julio Landero Figueroa, George S Deepe, Anne P Vonderheide
This work sought to assess optimal extraction conditions in the study of the metalloproteome of the dimorphic fungus Histoplasma capsulatum. One of the body's responses to H. capsulatum infection is sequestration of zinc within host macrophage (MØ), as reported by Vignesh et al. (Immunity 39:697-710, 2013) and Vignesh et al. (PLOS Pathog 9:E1003815, 2013). Thus, metalloproteins containing zinc were of greatest interest as it plays a critical role in survival of the fungus. One challenge in metalloproteomics is the preservation of the native structure of proteins to retain non-covalently bound metals...
August 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/28800743/an-itraq-based-proteomic-analysis-reveals-dysregulation-of-neocortical-synaptopodin-in-lewy-body-dementias
#17
Arnab Datta, Yuek Ling Chai, Jing Min Tan, Jasinda H Lee, Paul T Francis, Christopher P Chen, Siu Kwan Sze, Mitchell K P Lai
Lewy body dementias are the second most common cause of neurodegenerative dementia in the elderly after Alzheimer's disease (AD). The two clinical subgroups of Lewy body dementias, namely, dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), are differentiated by the chronology of cognitive symptoms relative to parkinsonism. At present, there remains a debate on whether DLB and PDD are separate disease entities, or fall within the same spectrum of Lewy body dementias. In this study, we compared the detergent-soluble proteome via an 8-plex isobaric tag for relative and absolute quantitation (iTRAQ) analysis of pooled lysates from the prefrontal cortex (BA9) of DLB (n = 19) and PDD (n = 21) patients matched a priori for amyloid (total Aβ42) burden, semi-quantitative scores for Lewy bodies and neurofibrillary tangles together with age-matched control (n = 21) subjects...
August 11, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28798667/the-foxp2-driven-network-in-developmental-disorders-and-neurodegeneration
#18
Franz Oswald, Patricia Klöble, André Ruland, David Rosenkranz, Bastian Hinz, Falk Butter, Sanja Ramljak, Ulrich Zechner, Holger Herlyn
The transcription repressor FOXP2 is a crucial player in nervous system evolution and development of humans and songbirds. In order to provide an additional insight into its functional role we compared target gene expression levels between human neuroblastoma cells (SH-SY5Y) stably overexpressing FOXP2 cDNA of either humans or the common chimpanzee, Rhesus monkey, and marmoset, respectively. RNA-seq led to identification of 27 genes with differential regulation under the control of human FOXP2, which were previously reported to have FOXP2-driven and/or songbird song-related expression regulation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28797586/obesity-as-defined-by-waist-circumference-but-not-body-mass-index-is-associated-with-higher-renal-mass-complexity
#19
Laura A Bertrand, Lewis J Thomas, Peng Li, Claire M Buchta, Shannon K Boi, Rachael M Orlandella, James A Brown, Kenneth G Nepple, Lyse A Norian
OBJECTIVES: Obesity, typically defined as a body mass index (BMI)≥30kg/m(2), is an established risk factor for renal cell carcinoma (RCC) but is paradoxically linked to less advanced disease at diagnosis and improved outcomes. However, BMI has inherent flaws, and alternate obesity-defining metrics that emphasize abdominal fat are available. We investigated 3 obesity-defining metrics, to better examine the associations of abdominal fat vs. generalized obesity with renal tumor stage, grade, or R...
August 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28797124/preclinical-development-of-a-vaccine-against-oligomeric-alpha-synuclein-based-on-virus-like-particles
#20
Marika Doucet, Aadil El-Turabi, Franziska Zabel, Benjamin H M Hunn, Nora Bengoa-Vergniory, Milena Cioroch, Mauricio Ramm, Amy M Smith, Ariane Cruz Gomes, Gustavo Cabral de Miranda, Richard Wade-Martins, Martin F Bachmann
Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies...
2017: PloS One
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