keyword
MENU ▼
Read by QxMD icon Read
search

synucleinopathy

keyword
https://www.readbyqxmd.com/read/28722658/the-golgi-localized-gamma-ear-containing-arf-binding-gga-protein-family-alters-alpha-synuclein-%C3%AE-syn-oligomerization-and-secretion
#1
Bjoern von Einem, Judith Eschbach, Martin Kiechle, Anke Wahler, Dietmar R Thal, Pamela J McLean, Jochen H Weishaupt, Albert C Ludolph, Christine A F von Arnim, Karin M Danzer
Several age-related neurodegenerative disorders are associated with protein misfolding and aggregation of toxic peptides. α-synuclein (α-syn) aggregation and the resulting cytotoxicity is a hallmark of Parkinson's disease (PD) as well as dementia with Lewy bodies. Rising evidence points to oligomeric and pre-fibrillar forms as the pathogenic species, and oligomer secretion seems to be crucial for the spreading and progression of PD pathology. Recent studies implicate that dysfunctions in endolysosomal/autophagosomal pathways increase α-syn secretion...
July 15, 2017: Aging
https://www.readbyqxmd.com/read/28713844/epidemiology-diagnosis-and-management-of-neurogenic-orthostatic-hypotension
#2
Jose-Alberto Palma, Horacio Kaufmann
BACKGROUND: Orthostatic hypotension (OH) is a sustained fall in blood pressure on standing which can cause symptoms of organ hypoperfusion. OH is associated with increased morbidity and mortality and leads to a significant number of hospital admissions particularly in the elderly (233 per 100,000 patients over 75 years of age in the US). OH can be due to volume depletion, blood loss, large varicose veins, medications, or due to defective activation of sympathetic nerves and reduced norepinephrine release upon standing (i...
May 2017: Movement Disorders Clinical Practice
https://www.readbyqxmd.com/read/28711409/nortriptyline-inhibits-aggregation-and-neurotoxicity-of-alpha-synuclein-by-enhancing-reconfiguration-of-the-monomeric-form
#3
Timothy J Collier, Kinshuk R Srivastava, Craig Justman, Tom Grammatopoulous, Birgit Hutter-Paier, Manuela Prokesch, Daniel Havas, Jean-Christophe Rochet, Fang Liu, Kevin Jock, Patrícia de Oliveira, Georgia L Stirtz, Ulf Dettmer, Caryl E Sortwell, Mel B Feany, Peter Lansbury, Lisa Lapidus, Katrina L Paumier
The pathology of Parkinson's disease and other synucleinopathies is characterized by the formation of intracellular inclusions comprised primarily of misfolded, fibrillar α-synuclein (α-syn). One strategy to slow disease progression is to prevent the misfolding and aggregation of its native monomeric form. Here we present findings that support the contention that the tricyclic antidepressant compound nortriptyline (NOR) has disease-modifying potential for synucleinopathies. Findings from in vitro aggregation and kinetics assays support the view that NOR inhibits aggregation of α-syn by directly binding to the soluble, monomeric form, and by enhancing reconfiguration of the monomer, inhibits formation of toxic conformations of the protein...
July 12, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28702747/management-of-supine-hypertension-complicating-neurogenic-orthostatic-hypotension
#4
Jacquie Baker, Kurt Kimpinski
Neurogenic orthostatic hypotension (NOH) can be present in a number of disorders, including synucleinopathies, autoimmune disorders, and various genetic disorders. All are characterized by defective norepinephrine release from sympathetic terminals upon standing, resulting in impaired vasoconstriction. NOH is defined as a drop in systolic blood pressure ≥20 mmHg or diastolic blood pressure ≥10 mmHg, or both, within 3 minutes of standing or head up-tilt at a minimum of 60°. However, approximately 50% of patients have associated supine hypertension, which greatly complicates treatment...
July 12, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28684246/imaging-neuroinflammation-to-monitor-%C3%AE-synucleinopathy
#5
Yasuomi Ouchi
No abstract text is available yet for this article.
July 3, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28684245/assessment-of-neuroinflammation-in-patients-with-idiopathic-rapid-eye-movement-sleep-behaviour-disorder-a-case-control-study
#6
Morten Gersel Stokholm, Alex Iranzo, Karen Østergaard, Mónica Serradell, Marit Otto, Kristina Bacher Svendsen, Alicia Garrido, Dolores Vilas, Per Borghammer, Joan Santamaria, Arne Møller, Carles Gaig, David J Brooks, Eduardo Tolosa, Nicola Pavese
BACKGROUND: Findings from longitudinal follow-up studies in patients with idiopathic rapid-eye-movement sleep behaviour disorder (IRBD) have shown that most patients will eventually develop the synucleinopathies Parkinson's disease, dementia with Lewy bodies, or multiple system atrophy. Neuroinflammation in the form of microglial activation is present in synucleinopathies and is a potential therapeutic target to halt or delay the neurodegenerative process. We aimed to investigate whether neuroinflammation is present in patients with IRBD and its possible relation to nigrostriatal dopamine function...
July 3, 2017: Lancet Neurology
https://www.readbyqxmd.com/read/28676257/baicalein-blocks-%C3%AE-synuclein-secretion-from-sn4741-cells-and-facilitates-%C3%AE-synuclein-polymerization-to-big-complex
#7
Xingjian Li, Guofeng Zhang, Qi Nie, Ting Wu, Luyan Jiao, Meige Zheng, Xiaomei Wan, Yonglin Li, Song Wu, Bin Jiang, Xianhong Xiang, Jinhai Duan, Xian Lin
The secretion of α-synuclein (α-syn) acts as an essential driver in the propagation of synucleinopathies in brain. The clearance of extracellular α-syn or blockade of the cell-to-cell transmission of α-syn is a promising approach to prohibiting synucleinopathies propagation. Baicalein (BAI), a flavonoid from Chinese herb, has been reported to bind covalently to α-syn to inhibit α-syn fibrillation and degrade its fibrils. However, whether BAI inhibits α-syn secretion is unclear. Here we showed that BAI reduced α-syn in the media of dopaminergic cell lines (SN4741) overexpressing wild-type α-syn (W-syn) or A53T mutant type α-syn (A53T-syn), while increased α-syn expression in cell lysates, upregulated the cell viability and increased the ratio of LC3 II/LC3 I, the latter is an indicator reflects the macroautophagic level...
July 1, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28676095/toll-like-receptor-4-stimulation-with-monophosphoryl-lipid-a-ameliorates-motor-deficits-and-nigral-neurodegeneration-triggered-by-extraneuronal-%C3%AE-synucleinopathy
#8
Serena Venezia, Violetta Refolo, Alexia Polissidis, Leonidas Stefanis, Gregor K Wenning, Nadia Stefanova
BACKGROUND: Alpha-synuclein (α-syn) aggregation represents the pathological hallmark of α-synucleinopathies like Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Toll-like receptors (TLRs) are a family of highly conserved molecules that recognize pathogen-associated molecular patterns and define the innate immunity response. It was previously shown that TLR4 plays a role in the clearance of α-syn, suggesting that TLR4 up-regulation in microglia may be a natural mechanism to improve the clearance of α-syn...
July 4, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28671665/asparagine-endopeptidase-cleaves-%C3%AE-synuclein-and-mediates-pathologic-activities-in-parkinson-s-disease
#9
Zhentao Zhang, Seong Su Kang, Xia Liu, Eun Hee Ahn, Zhaohui Zhang, Li He, P Michael Iuvone, Duc M Duong, Nicholas T Seyfried, Matthew J Benskey, Fredric P Manfredsson, Lingjing Jin, Yi E Sun, Jian-Zhi Wang, Keqiang Ye
Aggregated forms of α-synuclein play a crucial role in the pathogenesis of synucleinopathies such as Parkinson's disease (PD). However, the molecular mechanisms underlying the pathogenic effects of α-synuclein are not completely understood. Here we show that asparagine endopeptidase (AEP) cleaves human α-synuclein, triggers its aggregation and escalates its neurotoxicity, thus leading to dopaminergic neuronal loss and motor impairments in a mouse model. AEP is activated and cleaves human α-synuclein at N103 in an age-dependent manner...
July 3, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28655059/association-of-autonomic-dysfunction-with-disease-progression-and-survival-in-parkinson-disease
#10
Eduardo De Pablo-Fernandez, Carmen Tur, Tamas Revesz, Andrew J Lees, Janice L Holton, Thomas T Warner
Importance: Evidence suggests that development of autonomic dysfunction (AutD) may negatively affect disease course and survival in patients with synucleinopathies. However, the few available studies on Parkinson disease (PD) have conflicting results, comprise a small number of patients, have short follow-up periods, and lack pathologic confirmation of the diagnosis. Objective: To examine the association of time of onset of AutD with disease progression and survival in PD...
June 26, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28652595/altered-brain-metabolic-connectivity-at-multiscale-level-in-early-parkinson-s-disease
#11
Arianna Sala, Silvia Paola Caminiti, Luca Presotto, Enrico Premi, Andrea Pilotto, Rosanna Turrone, Maura Cosseddu, Antonella Alberici, Barbara Paghera, Barbara Borroni, Alessandro Padovani, Daniela Perani
To explore the effects of PD pathology on brain connectivity, we characterized with an emergent computational approach the brain metabolic connectome using [18F]FDG-PET in early idiopathic PD patients. We applied whole-brain and pathology-based connectivity analyses, using sparse-inverse covariance estimation in thirty-four cognitively normal PD cases and thirty-four age-matched healthy subjects for comparisons. Further, we assessed high-order resting state networks by interregional correlation analysis. Whole-brain analysis revealed altered metabolic connectivity in PD, with local decreases in frontolateral cortex and cerebellum and increases in the basal ganglia...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28649596/phenoconversion-from-probable-rapid-eye-movement-sleep-behavior-disorder-to-mild-cognitive-impairment-to-dementia-in-a-population-based-sample
#12
Youngsin Jung, Brendon P Boot, Michelle M Mielke, Tanis J Ferman, Yonas E Geda, Eric McDade, Teresa J H Christianson, David S Knopman, Erik K St Louis, Michael H Silber, Ronald C Petersen, Bradley F Boeve
INTRODUCTION: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with synucleinopathies. In 2012, we reported an increased risk of mild cognitive impairment (MCI) and Parkinson disease (PD) in cognitively normal Olmsted County, Minnesota, residents, aged 70 to 89 years with probable RBD. Here, we examine their progression to dementia and other neurodegenerative phenotypes. METHODS: Fifteen participants with RBD who were diagnosed with either MCI or PD were longitudinally followed, and their subsequent clinical courses were reviewed...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28648742/polo-like-kinase-2-modulates-%C3%AE-synuclein-protein-levels-by-regulating-its-mrna-production
#13
Rikke H Kofoed, Jin Zheng, Nelson Ferreira, Søren Lykke-Andersen, Mauro Salvi, Cristine Betzer, Lasse Reimer, Torben Heick Jensen, Karina Fog, Poul H Jensen
Variations in the α-synuclein-encoding SNCA gene represent the greatest genetic risk factor for Parkinson's disease (PD), and duplications/triplications of SNCA cause autosomal dominant familial PD. These facts closely link brain levels of α-synuclein with the risk of PD, and make lowering α-synuclein levels a therapeutic strategy for the treatment of PD and related synucleinopathies. In this paper, we corroborate previous findings on the ability of overexpressed Polo-like kinase 2 (PLK-2) to decrease cellular α-synuclein, but demonstrate that the process is independent of PLK-2 phosphorylating S129 in α-synuclein because a similar reduction is achieved with the non-phosphorable S129A mutant α-synuclein...
June 23, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28645308/neonatal-aav-delivery-of-alpha-synuclein-induces-pathology-in-the-adult-mouse-brain
#14
Marion Delenclos, Ayman H Faroqi, Mei Yue, Aishe Kurti, Monica Castanedes-Casey, Linda Rousseau, Virginia Phillips, Dennis W Dickson, John D Fryer, Pamela J McLean
Abnormal accumulation of alpha-synuclein (αsyn) is a pathological hallmark of Lewy body related disorders such as Parkinson's disease and Dementia with Lewy body disease. During the past two decades, a myriad of animal models have been developed to mimic pathological features of synucleinopathies by over-expressing human αsyn. Although different strategies have been used, most models have little or no reliable and predictive phenotype. Novel animal models are a valuable tool for understanding neuronal pathology and to facilitate development of new therapeutics for these diseases...
June 23, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28639878/exploring-the-phenotype-in-mild-cognitive-impairment-to-aid-the-prediction-of-those-at-risk-of-transitioning-to-parkinson-disease-and-dementia-with-lewy-bodies
#15
Jennifer Y Y Szeto, Glenda M Halliday, Sharon L Naismith, Simon J G Lewis
To date, only limited research has concurrently investigated the presence of rapid eye movement sleep behavior disorder (RBD) and other features associated with Parkinson disease (PD) and dementia with Lewy bodies (DLB) in people presenting with mild cognitive impairment (MCI). As a first step towards a longitudinal research project, the present study explored the relationships between MCI, RBD, and depression in 108 older adults who presented with subjective memory complaints but were not known to have a neurodegenerative condition...
July 2017: Journal of Geriatric Psychiatry and Neurology
https://www.readbyqxmd.com/read/28637099/aggregation-and-phosphorylation-of-%C3%AE-synuclein-with-proteinase-k-resistance-in-focal-%C3%AE-synucleinopathy-predominantly-localized-to-the-cardiac-sympathetic-nervous-system
#16
Nei Fukasawa, Takahiro Fukuda, Masato Nagaoka, Tohru Harada, Hiroyuki Takahashi, Masahiro Ikegami
Aggregates of α-synuclein, a major component of Lewy bodies (LBs) and Lewy neurites (LNs), are distributed throughout the nervous system, including the central nervous system (CNS), sympathetic ganglia, enteric nervous system (ENS), cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin, in incidental Lewy body disease (ILBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), and pure autonomic failure (PAF) [1-3]. Here we report focal α-synucleinopathy predominantly localized to the cardiac sympathetic nervous system (SNS)...
June 21, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28622212/a-retrospective-study-of-pimavanserin-use-in-a-movement-disorders-clinic
#17
Joseph H Friedman
Pimavanserin, a 5-HT2A inverse agonist, was commercially released in the United States in April 2016 for the treatment of Parkinson disease psychosis. No "naturalistic" treatment results have yet been published. Charts from the movement disorders clinic were reviewed for all patients who received this drug as treatment for psychosis associated with primary parkinsonism due to α-synucleinopathies. Data of 10 patients with idiopathic Parkinson disease, including 1 with a long history of schizophrenia, 4 with dementia with Lewy bodies, and 1 with multiple-system atrophy, were reviewed...
July 2017: Clinical Neuropharmacology
https://www.readbyqxmd.com/read/28611062/selective-imaging-of-internalized-proteopathic-%C3%AE-synuclein-seeds-in-primary-neurons-reveals-mechanistic-insight-into-transmission-of-synucleinopathies
#18
Richard J Karpowicz, Conor M Haney, Tiberiu S Mihaila, Raizel M Sandler, E James Petersson, Virginia M-Y Lee
Direct cell-to-cell transmission of proteopathic alpha-synuclein (α-syn) aggregates is thought to underlie the progression of neurodegenerative synucleinopathies. However, the specific intracellular processes governing this transmission remain unclear because currently-available model systems are limited. For example, in cell culture models of α-syn-seeded aggregation, it is difficult to discern intracellular from extracellular exogenously applied α-syn seed species. Herein, we employed fluorescently labeled α-syn preformed fibrils (pffs) in conjunction with the membrane-impermeable fluorescence quencher trypan blue to selectively image internalized α-syn seeds in cultured primary neurons and to quantitatively characterize the concentration dependence, time course, and inhibition of pff uptake...
June 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28596752/the-retina-in-multiple-system-atrophy-systematic-review-and-meta-analysis
#19
REVIEW
Carlos E Mendoza-Santiesteban, Iñigo Gabilondo, Jose Alberto Palma, Lucy Norcliffe-Kaufmann, Horacio Kaufmann
BACKGROUND: Multiple system atrophy (MSA) is a rare, adult-onset, rapidly progressive fatal synucleinopathy that primarily affects oligodendroglial cells in the brain. Patients with MSA only rarely have visual complaints, but recent studies of the retina using optical coherence tomography (OCT) showed atrophy of the peripapillary retinal nerve fiber layer (RNFL) and to a lesser extent the macular ganglion cell layer (GCL) complex. METHODS: We performed a literature review and meta-analysis according to the preferred reporting items for systematic reviews and meta-analyses guidelines for studies published before January 2017, identified through PubMed and Google Scholar databases, which reported OCT-related outcomes in patients with MSA and controls...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28595550/new-tracers-and-new-perspectives-for-molecular-imaging-in-lewy-body-diseases
#20
Matteo Bauckneht, Dario Arnaldi, Flavio Nobili, Dag Aarsland, Silvia Morbelli
The term Lewy body diseases (LBDs) refers to a subset of neurodegenerative disorders that share the accumulation of the so-called Lewy bodies (LB) including: Parkinson's disease (PD), dementia with Lewy bodies (DLB), and PD later characterized by the occurrence of dementia (PDD). Moreover, multiple system atrophy (MSA) and idiopatic Rem Sleeping behaviour disorders (RBD) complete the group of synucleinopathies and have also common symptoms with respect to LBDs. The clinical diagnosis of LBDs can be challenging for physicians, particularly in the early stages of disease...
June 8, 2017: Current Medicinal Chemistry
keyword
keyword
39701
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"