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Multiple systems atrophy

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https://www.readbyqxmd.com/read/29150334/a-routinely-used-protein-staining-dye-acts-as-an-inhibitor-of-wild-type-and-mutant-alpha-synuclein-aggregation-and-modulator-of-neurotoxicity
#1
Nuzhat Ahsan, Ibrar Ahmed Siddique, Sarika Gupta, Avadhesha Surolia
Inhibition of amyloid formation along with modulation of toxicity employing small molecules is emerging as a potential therapeutic approach for protein misfolding disorders which includes Parkinson's disease, Alzheimer's disease and Multiple System Atrophy etc. Countless current interventional strategies for treating α-synucleinopathies consider using peptidic and non-peptidic inhibitors for arresting fibrillisation, disrupting existing fibrils and reducing associated toxicity. One group of molecules less exploited in this regard are triphenylmethane dyes...
October 12, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29149290/discovering-the-3-utr-mediated-regulation-of-alpha-synuclein
#2
Domenica Marchese, Teresa Botta-Orfila, Davide Cirillo, Juan Antonio Rodriguez, Carmen Maria Livi, Rubén Fernández-Santiago, Mario Ezquerra, Maria J Martí, Elias Bechara, Gian Gaetano Tartaglia
Recent evidence indicates a link between Parkinson's Disease (PD) and the expression of a-synuclein (SNCA) isoforms with different 3' untranslated regions (3'UTRs). Yet, the post-transcriptional mechanisms regulating SNCA expression are unknown. Using a large-scale in vitro/in silico screening we identified RNA-binding proteins (RBPs) that interact with SNCA 3' UTRs. We identified two RBPs, ELAVL1 and TIAR, that bind with high affinity to the most abundant and translationally active 3' UTR isoform (575 nt)...
November 15, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29148965/nonclinical-safety-assessment-of-anti-factor-d-key-strategies-and-challenges-for-the-nonclinical-development-of-intravitreal-biologics
#3
Vladimir Bantseev, Rebecca Erickson, Douglas Leipold, Caroline Amaya, Paul E Miller, Helen Booler, Evan A Thackaberry
PURPOSE: The nonclinical toxicology program described here was designed to characterize the safety profile of anti-factor D (AFD; FCFD4514S, lampalizumab) to support intravitreal (ITV) administration in patients with geographic atrophy (GA). METHODS: The toxicity of AFD was assessed in a single-dose and 6-month repeat-dose study in monkeys at doses up to 10 mg/eye. Toxicity was assessed by clinical ophthalmic examinations, intraocular pressure measurements, ocular photography, electroretinography, fluorescein angiography, optical coherence tomography, and anatomic pathology...
November 17, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29147836/effects-of-saffron%C3%A2-and-its-constituents-%C3%A2-crocin-1-crocin-2-and-crocetin-on-%C3%AE-synuclein-fibrils
#4
Eiji Inoue, Yasuharu Shimizu, Ryo Masui, Tomomi Hayakawa, Tomoe Tsubonoya, Satoko Hori, Keiichi Sudoh
Saffron, the stigma of Crocus sativus Linné (Iridaceae family), has been known to inhibit aggregation of β-amyloid, a nerve tissue protein. α-Synuclein (αS) is a 140-amino acid protein found abundantly in various regions of the brain. Its abnormal aggregation and accumulation in nerve tissue are said to cause neurodegenerative diseases such as Parkinson's disease, Lewy body dementia, and multiple-system atrophy. This study (part of this study was presented at the 137th Annual Meeting of the Pharmaceutical Society of Japan) examined the effects of saffron, its constituents (crocin-1, crocin-2, crocetin, and safranal), and crocetin structural analogs (hexadecanedioic acid, norbixin, and trans, trans-muconic acid) on αS aggregation, and αS fibril dissociation...
November 17, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/29145182/pathological-yawning-laughing-and-crying
#5
Olivier Walusinski
Yawning, laughing, and crying are normal physiological behaviors of humans in good health. As with all physiological behaviors, their deregulation can reveal disorders. Pathological yawning occurs in salvos of 10-20 successive yawns, and the number of yawns per day can exceed one hundred. After listing the functional etiologies, we will give the clinical keys for differentiating the most serious causes: iatrogenic, tumors, strokes, amyotrophic lateral sclerosis, and intracranial hypertension. Sudden, uncontrollable episodes of emotional display involving pathological laughing and crying (PLC) may be encountered in various neurological diseases: amyotrophic lateral sclerosis, multiple system atrophy (cerebellar), cerebrovascular disease, traumatic brain injuries, mass lesions in the cerebellopontine junction, and epilepsy...
2018: Frontiers of Neurology and Neuroscience
https://www.readbyqxmd.com/read/29143287/lipoic-acid-stimulates-camp-production-in-healthy-control-and-secondary-progressive-ms-subjects
#6
Sarah E Fiedler, Vijayshree Yadav, Amelia R Kerns, Catherine Tsang, Sheila Markwardt, Edward Kim, Rebecca Spain, Dennis Bourdette, Sonemany Salinthone
Lipoic acid (LA) exhibits antioxidant and anti-inflammatory properties; supplementation reduces disease severity and T lymphocyte migration into the central nervous system in a murine model of multiple sclerosis (MS), and administration in secondary progressive MS (SPMS) subjects reduces brain atrophy compared to placebo. The mechanism of action (MOA) of LA's efficacy in suppression of MS pathology is incompletely understood. LA stimulates production of the immunomodulator cyclic AMP (cAMP) in vitro. To determine whether cAMP could be involved in the MOA of LA in vivo, we performed a clinical trial to examine whether LA stimulates cAMP production in healthy control and MS subjects, and whether there are differences in the bioavailability of LA between groups...
November 15, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128630/association-analysis-of-snp-rs11868035-in-srebf1-with-sporadic-parkinson-s-disease-sporadic-amyotrophic-lateral-sclerosis-and-multiple-system-atrophy-in-a-chinese-population
#7
Xiao Qin Yuan, Bei Cao, Ying Wu, Yong Ping Chen, Qian Qian Wei, Ru Wei Ou, Jing Yang, Xue Ping Chen, Bi Zhao, Wei Song, Hui Fang Shang
BACKGROUND: The etiology of neurodegenerative disease remains unclear. Recently, SNP rs11868035, located in an intron of the sterol regulatory element binding factor (SREBF1) gene, was found to be associated with Parkinson's disease (PD) in a large European population in a genome-wide association study. To examine the possible genetic association of rs11868035 with sporadic PD, sporadic amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA) in a Chinese population, we conducted this large case-control study...
November 8, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29126761/mr-planimetry-in-neurodegenerative-parkinsonism-yields-high-diagnostic-accuracy-for-psp
#8
Stephanie Mangesius, Anna Hussl, Florian Krismer, Philipp Mahlknecht, Eva Reiter, Susanne Tagwercher, Atbin Djamshidian, Michael Schocke, Regina Esterhammer, Gregor Wenning, Christoph Müller, Christoph Scherfler, Elke R Gizewski, Werner Poewe, Klaus Seppi
INTRODUCTION: Several previous studies examined different brainstem-derived MR planimetric measures with regards to their diagnostic accuracy in separating patients with neurodegenerative parkinsonian disorders and reported conflicting results. The current study aimed to compare their performance in a well-characterized sample of patients with neurodegenerative parkinsonian disorders. METHODS: MR planimetric measurements were assessed in a large retrospective cohort of 55 progressive supranuclear palsy (PSP), 194 Parkinson's disease (PD) and 63 multiple system atrophy (MSA) patients...
October 31, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29124503/urological-dysfunction-in-synucleinopathies-epidemiology-pathophysiology-and-management
#9
REVIEW
Ryuji Sakakibara, Fuyuki Tateno, Tatsuya Yamamoto, Tomoyuki Uchiyama, Tomonori Yamanishi
OBJECTIVE: Parkinson's disease (PD) and multiple system atrophy (MSA) are major neurogenerative diseases characterized pathologically by abnormal alpha-synuclein aggregation. PD and MSA are clinically characterized by motor disorder and bladder dysfunction (mainly urinary urgency and frequency, also called overactive bladder). However, few literatures are available concerning bladder dysfunction in PD or MSA. METHOD: A systematic review. RESULTS: The bladder dysfunction in MSA is more severe than that in PD for large post-void residual or urinary retention...
November 9, 2017: Clinical Autonomic Research: Official Journal of the Clinical Autonomic Research Society
https://www.readbyqxmd.com/read/29121642/limbic-system-damage-in-ms-mri-assessment-and-correlations-with-clinical-testing
#10
Jie Wen, Dmitriy A Yablonskiy, Amber Salter, Anne H Cross
Volume loss in some limbic region structures has been observed in multiple sclerosis (MS) patients. However, in vivo evaluation of existing tissue cellular microstructure integrity has received less attention. The goal of studies reported here was to quantitatively assess loss of limbic system volumes and tissue integrity, and to evaluate associations of these measures with cognitive and physical dysfunction in MS patients. Thirty-one healthy controls (HC) and 80 MS patients, including 32 relapsing remitting (RRMS), 32 secondary progressive (SPMS) and 16 primary progressive (PPMS), participated in this study...
2017: PloS One
https://www.readbyqxmd.com/read/29119326/neurodegeneration-and-the-ordered-assembly-of-%C3%AE-synuclein
#11
REVIEW
Maria Grazia Spillantini, Michel Goedert
In 2017, it was 200 years since James Parkinson published 'An Essay on the Shaking Palsy' and 20 years since α-synuclein aggregation came to the fore. In 1998, multiple system atrophy joined Parkinson's disease and dementia with Lewy bodies as the third major synucleinopathy. Here, we describe the work that led to the identification of α-synuclein in Lewy bodies, Lewy neurites and Papp-Lantos bodies. We also review some of the findings reported since 1997.
November 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29118735/divergent-thinking-in-parkinsonism-a-case-control-study
#12
Margherita Canesi, Maria Luisa Rusconi, Emanuele Cereda, Alessandra Ranghetti, Viviana Cereda, Federica Moroni, Gianni Pezzoli
Background: Creativity is a multidimensional phenomenon and an important component of human capacities. This ability is characterized by the involvement of several cognitive functions particularly linked to the prefrontal cortex. We compared divergent thinking, a measure of creativity, in patients affected by progressive supranuclear palsy (PSP), other parkinsonian syndromes, and healthy controls (HCs). Methods: Creativity features were evaluated using the Abbreviated Torrance Test for Adults (ATTA)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29116402/a-critical-review-of-the-prion-hypothesis-of-human-synucleinopathies
#13
REVIEW
Gültekin Tamgüney, Amos D Korczyn
Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) are neurodegenerative disorders which have been pathologically classified as synucleinopathies, since they are associated with pathognomonic deposits of misfolded alpha-synuclein in cells of the nervous system. Recently PD, DLB, and MSA were also suggested to be prion-like disorders. Much controversy exists regarding this analogy between synucleinopathies and prion diseases. Here, we discuss what characterizes prion diseases and in which way synucleinopathies may be considered prion-like or -unlike...
November 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/29115515/serum-microrna-expression-profiling-in-patients-with-multiple-system-atrophy
#14
Kodai Kume, Hisakazu Iwama, Kazushi Deguchi, Kazuyo Ikeda, Tadayuki Takata, Yohei Kokudo, Masaki Kamada, Keiko Fujikawa, Kayo Hirose, Hisashi Masugata, Tetsuo Touge, Tsutomu Masaki
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that is pathologically characterized by α‑synuclein positive glial cytoplasmic inclusions in oligodendrocytes. The clinical diagnosis of MSA is often challenging as there are no established biomarkers and diagnoses are now based on clinical findings alone. At present, the etiology and pathogenesis of MSA are unclear. It has been reported that dysregulation of microRNA (miRNA/miR) serves an important role in neurodegenerative disorders including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis...
November 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29111419/diagnosis-of-multiple-system-atrophy
#15
REVIEW
Jose-Alberto Palma, Lucy Norcliffe-Kaufmann, Horacio Kaufmann
Multiple system atrophy (MSA) may be difficult to distinguish clinically from other disorders, particularly in the early stages of the disease. An autonomic-only presentation can be indistinguishable from pure autonomic failure. Patients presenting with parkinsonism may be misdiagnosed as having Parkinson disease. Patients presenting with the cerebellar phenotype of MSA can mimic other adult-onset ataxias due to alcohol, chemotherapeutic agents, lead, lithium, and toluene, or vitamin E deficiency, as well as paraneoplastic, autoimmune, or genetic ataxias...
October 23, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/29109891/adipose-tissue-autophagy-and-homeostasis-in-alcohol-induced-liver-injury
#16
Yuan Li, Wen-Xing Ding
Alcohol consumption leads to injury in multiple organs and systems, including the liver, brain, heart, skeletal muscle, pancreas, bone, immune system, and endocrine system. Emerging evidence indicates that alcohol also promotes adipose tissue dysfunction, which may contribute to injury progression in other organs and systems. Autophagy is a lysosomal degradation pathway that has been shown to regulate adipose tissue homeostasis and adipogenesis. Increasing evidence also demonstrates that alcohol consumption affects autophagy in multiple tissues...
June 2017: Liver Res
https://www.readbyqxmd.com/read/29107645/cerebrospinal-fluid-levels-of-coenzyme-q10-are-reduced-in-multiple-system-atrophy
#17
Yaroslau Compta, Darly M Giraldo, Esteban Muñoz, Francesca Antonelli, Manel Fernández, Paloma Bravo, Marta Soto, Ana Cámara, Ferran Torres, María José Martí
INTRODUCTION: The finding of mutations of the COQ2 gene and reduced coenzyme Q10 levels in the cerebellum in multiple system atrophy (MSA) suggest that coenzyme Q10 is relevant to MSA pathophysiology. Two recent studies have reported reduced coenzyme Q10 levels in plasma and serum (respectively) of MSA patients compared to Parkinson's disease and/or control subjects, but with largely overlapping values, limited comparison with other parkinsonisms, or dependence on cholesterol levels. We hypothesized that cerebrospinal fluid (CSF) is reliable to assess reductions in coenzyme Q10 as a candidate biomarker of MSA...
October 20, 2017: Parkinsonism & related Disorders
https://www.readbyqxmd.com/read/29104019/symptomatic-therapy-of-multiple-system-atrophy
#18
REVIEW
Guido Rohrer, Günter U Höglinger, Johannes Levin
Multiple system atrophy is a progressive neurodegenerative disease characterized by the association of autonomic failure and a movement disorder that consist of either a hypokinetic movement disorder or a cerebellar syndrome or both. In addition to these core characteristics other movement disorders (e.g. dystonia, myoclonus, spasticity), and neuropsychiatric symptoms (e.g. depression, cognitive dysfunction) may occur in the course of the disease and can severely impair patients' quality of live. To date no causal therapy is available and therefore symptomatic treatment plays a pivotal role in patient care...
October 27, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/29101940/rem-sleep-behavior-disorder-diagnosis-clinical-implications-and-future-directions
#19
REVIEW
Erik K St Louis, Bradley F Boeve
Rapid eye movement sleep behavior disorder (RBD) is diagnosed by a clinical history of dream enactment accompanied by polysomnographic rapid eye movement sleep atonia loss (rapid eye movement sleep without atonia). Rapid eye movement sleep behavior disorder is strongly associated with neurodegenerative disease, especially synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. A history of RBD may begin several years to decades before onset of any clear daytime symptoms of motor, cognitive, or autonomic impairments, suggesting that RBD is the presenting manifestation of a neurodegenerative process...
November 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/29098660/therapeutic-potential-of-ursolic-acid-to-manage-neurodegenerative-and-psychiatric-diseases
#20
Ana B Ramos-Hryb, Francis L Pazini, Manuella P Kaster, Ana Lúcia S Rodrigues
Ursolic acid is a pentacyclic triterpenoid found in several plants. Despite its initial use as a pharmacologically inactive emulsifier in pharmaceutical, cosmetic and food industries, several biological activities have been reported for this compound so far, including anti-tumoural, anti-diabetic, cardioprotective and hepatoprotective properties. The biological effects of ursolic acid have been evaluated in vitro, in different cell types and against several toxic insults (i.e. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, amyloid-β peptides, kainic acid and others); in animal models of brain-related disorders (Alzheimer disease, Parkinson disease, depression, traumatic brain injury) and ageing; and in clinical studies with cancer patients and for muscle atrophy...
November 2, 2017: CNS Drugs
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