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Lewy body disease

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https://www.readbyqxmd.com/read/28820063/loss-in-toxic-function-of-aggregates-of-%C3%AE-synuclein-mutants-by-a-%C3%AE-synuclein-derived-peptide
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/28805588/weight-in-parkinson-s-disease-phenotypical-significance
#7
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
#8
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/28800743/an-itraq-based-proteomic-analysis-reveals-dysregulation-of-neocortical-synaptopodin-in-lewy-body-dementias
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28794446/impaired-endo-lysosomal-membrane-integrity-accelerates-the-seeding-progression-of-%C3%AE-synuclein-aggregates
#13
Peizhou Jiang, Ming Gan, Shu-Hui Yen, Pamela J McLean, Dennis W Dickson
In neurodegenerative diseases, seeding is a process initiated by the internalization of exogenous protein aggregates. Multiple pathways for internalization of aggregates have been proposed, including direct membrane penetration and endocytosis. To decipher the seeding mechanisms of alpha-synuclein (αS) aggregates in human cells, we visualized αS aggregation, endo-lysosome distribution, and endo-lysosome rupture in real-time. Our data suggest that exogenous αS can seed endogenous cytoplasmic αS by either directly penetrating the plasma membrane or via endocytosis-mediated endo-lysosome rupture, leading to formation of endo-lysosome-free or endo-lysosome-associated αS aggregates, respectively...
August 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780707/evidence-for-association-between-hepatitis-c-virus-and-parkinson-s-disease
#14
REVIEW
Abdelrahman Ibrahim Abushouk, Mostafa Wanees Ahmed El-Husseny, Mayar Magdy, Ammar Ismail, Attia Attia, Hussien Ahmed, Ravikishore Pallanti, Ahmed Negida
Parkinson's disease (PD) is a globally prevalent neurodegenerative disorder, characterized by progressive neuronal loss in the substantia nigra and formation of Lewy bodies. These pathological characteristics are clinically translated into motor symptoms, such as bradykinesia, rigidity, resting tremors, and postural instability. Emerging data from epidemiological studies suggest a possible association between PD and hepatitis C virus (HCV) infection, which affects up to 71 million individuals worldwide. Preclinical studies have shown that HCV can penetrate and replicate within the brain macrophages and microglial cells, increasing their production of pro-inflammatory cytokines that can directly cause neuronal toxicity...
August 5, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28780180/neuropathology-of-parkinson-disease
#15
Dennis W Dickson
INTRODUCTION: Parkinson's disease (PD) is characterized by bradykinesia, rigidity, postural instability and tremor. Several pathologic processes can produce this syndrome, but neurodegeneration accompanied by neuronal inclusions composed of α-synuclein (Lewy bodies) is considered the typical pathologic correlate of PD. METHODS: The neuropathologic features of PD are reviewed based upon personal experience and review of the literature. Molecular pathology of PD is summarized from cell biological and animal studies...
August 1, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28780169/the-pmr1-pump-in-alpha-synuclein-toxicity-and-neurodegeneration
#16
REVIEW
Vassiliki Nikoletopoulou, Nektarios Tavernarakis
Proteinopathies constitute a diverse group of devastating neurodegenerative disorders, characterized by aberrant aggregation of specific proteins within neurons and in the brain parenchyma. Parkinson's disease (PD) is among the most common proteinopathies, caused by the accumulation of different species of α-synuclein and the formation of protein inclusions known as Lewy bodies. Although several mutations in the α-synuclein gene have been linked to PD, the mechanisms mediating the aggregation and toxicity of α-synuclein are not fully understood...
August 2, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28770235/respiratory-muscle-dysfunction-in-animal-models-of-hypoxic-disease-antioxidant-therapy-goes-from-strength-to-strength
#17
REVIEW
Ken D O'Halloran, Philip Lewis
The striated muscles of breathing play a critical role in respiratory homeostasis governing blood oxygenation and pH regulation. Upper airway dilator and thoracic pump muscles retain a remarkable capacity for plasticity throughout life, both in health and disease states. Hypoxia, whatever the cause, is a potent driver of respiratory muscle remodeling with evidence of adaptive and maladaptive outcomes for system performance. The pattern, duration, and intensity of hypoxia are key determinants of respiratory muscle structural-, metabolic-, and functional responses and adaptation...
2017: Hypoxia
https://www.readbyqxmd.com/read/28764902/experimental-animal-models-of-parkinson-s-disease-a-transition-from-assessing-symptomatology-to-%C3%AE-synuclein-targeted-disease-modification
#18
REVIEW
Wai Kin D Ko, Erwan Bezard
With the understanding that α-synuclein plays a major role in the pathogenesis of Parkinson's disease (PD), novel animal models have been developed for conducting preclinical research in screening novel disease modifying therapies. Advancements in research techniques in α-synuclein targeted disease modification have utilised methods such as viral mediated expression of human α-synuclein, as well as the inoculation of pathogenic α-synuclein species from Lewy Bodies of PD patients, for accurately modelling progressive self-propagating neurodegeneration...
July 29, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28756177/dementia-with-lewy-bodies-and-parkinson-s-disease-dementia-become-the-same-disease
#19
Joseph H Friedman
INTRODUCTION: The question whether DLB and PDD are distinct disorders has been debated in several forums. The two disorders, once parkinsonism is present in DLB, cannot be distinguished on clinical or pathological grounds. The conundrum exists for those DLB patients who do not yet have parkinsonism, and raises the parallel with patients who have Rapid Eye Movement Behavior Disorder but have not yet manifested parkinsonian signs. METHODS: A literature review was summarized to justify classification as a single disorder...
July 18, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/28751258/distinct-%C3%AE-synuclein-strains-and-implications-for-heterogeneity-among-%C3%AE-synucleinopathies
#20
REVIEW
Chao Peng, Ronald J Gathagan, Virginia M-Y Lee
The deposition of misfolded β-sheet enriched amyloid protein is a shared feature of many neurodegenerative diseases. Recent studies demonstrated the existence of conformationally diverse strains as a common property for multiple amyloidogenic proteins including α-Synuclein (α-Syn). α-Syn is misfolded and aggregated in a group of neurodegenerative diseases collectively known as α-Synucleinopathies, which include Parkinson's disease (PD), dementia with Lewy body, multiple system atrophy and also a subset of Alzheimer's disease patients with concomitant PD-like Lewy bodies and neurites...
July 24, 2017: Neurobiology of Disease
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