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https://www.readbyqxmd.com/read/29149290/discovering-the-3-utr-mediated-regulation-of-alpha-synuclein
#1
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/29147836/effects-of-saffron%C3%A2-and-its-constituents-%C3%A2-crocin-1-crocin-2-and-crocetin-on-%C3%AE-synuclein-fibrils
#2
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/29146111/microrna-expression-patterns-in-human-anterior-cingulate-and-motor-cortex-a-study-of-dementia-with-lewy-bodies-cases-and-controls
#3
Peter T Nelson, Wang-Xia Wang, Sarah A Janse, Katherine L Thompson
OVERVIEW: MicroRNAs (miRNAs) have been implicated in neurodegenerative diseases including Parkinson's disease and Alzheimer's disease (AD). Here, we evaluated the expression of miRNAs in anterior cingulate (AC; Brodmann area [BA] 24) and primary motor (MO; BA 4) cortical tissue from aged human brains in the University of Kentucky AD Center autopsy cohort, with a focus on dementia with Lewy bodies (DLB). METHODS: RNA was isolated from gray matter of brain samples with pathology-defined DLB, AD, AD+DLB, and low-pathology controls, with n=52 cases initially included (n=23 with DLB), all with low (<4hrs) postmortem intervals...
November 13, 2017: Brain Research
https://www.readbyqxmd.com/read/29143358/melatonin-improves-survival-and-respiratory-activity-of-yeast-cells-challenged-by-alpha-synuclein-and-menadione
#4
Mariana A Zampol, Mario H Barros
One of the hallmarks of Parkinson disease is α-synuclein aggregate deposition that leads to ER stress, Golgi fragmentation, and impaired energy metabolism with consequent redox imbalance. In the last decade, many studies have used Saccharomyces cerevisiae as a model in order to explore the intracellular consequences of α-synuclein overexpression. In this study we propose to evaluate the respiratory outcome of yeast cells expressing α-synuclein. Cell viability, or growth on selective media for respiratory activity was mainly affected in the α-synuclein expressing cells if they were also treated with menadione, which stimulates ROS production...
November 16, 2017: Yeast
https://www.readbyqxmd.com/read/29141588/parkinson-disease-polygenic-risk-score-is-associated-with-parkinson-disease-status-and-age-at-onset-but-not-with-alpha-synuclein-cerebrospinal-fluid-levels
#5
Laura Ibanez, Umber Dube, Benjamin Saef, John Budde, Kathleen Black, Alexandra Medvedeva, Jorge L Del-Aguila, Albert A Davis, Joel S Perlmutter, Oscar Harari, Bruno A Benitez, Carlos Cruchaga
BACKGROUND: The genetic architecture of Parkinson's Disease (PD) is complex and not completely understood. Multiple genetic studies to date have identified multiple causal genes and risk loci. Nevertheless, most of the expected genetic heritability remains unexplained. Polygenic risk scores (PRS) may provide greater statistical power and inform about the genetic architecture of multiple phenotypes. The aim of this study was to test the association between PRS and PD risk, age at onset and cerebrospinal fluid (CSF) biomarkers (α-synuclein, Aβ1-42, t-tau and p-tau)...
November 15, 2017: BMC Neurology
https://www.readbyqxmd.com/read/29137980/interaction-of-alpha-synuclein-with-cytogaligin-a-protein-encoded-by-the-proapoptotic-gene-galig
#6
Saïd El Haddad, Amandine Serrano, Thierry Normand, Chloé Robin, Martine Dubois, Fabienne Brule-Morabito, Lucile Mollet, Stéphane Charpentier, Alain Legrand
GALIG, an internal gene to the human galectin-3 gene, encodes two distinct proteins, Mitogaligin and Cytogaligin through translation of a unique mRNA in two overlapping alternative reading frames. When overexpressed GALIG induces apoptosis. In cultured cells, Mitogaligin destabilizes mitochondria membranes through interaction with cardiolipin. Little is known regarding the role of Cytogaligin. This protein displays multiple subcellular localizations; cytosol, nucleus, and mitochondria. We illustrate here that Cytogaligin is also secreted in the extracellular medium...
November 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29137975/microarray-analysis-of-an-synthetic-%C3%AE-synuclein-induced-cellular-model-reveals-the-expression-profile-of-long-non-coding-rna-in-parkinson-s-disease
#7
D Lin, Y Liang, X Jing, Y Chen, M Lei, Z Zeng, T Zhou, X Wu, S Peng, D Zheng, K Huang, L Yang, S Xiao, J Liu, E Tao
Long non-coding RNAs (lncRNAs) are a new research focus that are reported to influence the pathogenetic process of neurodegenerative disorders. To uncover new disease-associated genes and their relevant mechanisms, we carried out a gene microarray analysis based on a Parkinson's disease (PD) in vitro model induced by α-synuclein oligomers. This cellular model induced by 25 μmol/L α-synuclein oligomers has been confirmed to show the stable, transmissible neurotoxicity of α-synuclein, a typical PD pathological marker...
November 11, 2017: Brain Research
https://www.readbyqxmd.com/read/29136779/juglanin-ameliorates-lps-induced-neuroinflammation-in-animal-models-of-parkinson-s-disease-and-cell-culture-via-inactivating-tlr4-nf-%C3%AE%C2%BAb-pathway
#8
Fang-Xue Zhang, Ren-Shi Xu
Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid β (Aβ) and p-Tau...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#9
REVIEW
Karim Belarbi, Elodie Cuvelier, Alain Destée, Bernard Gressier, Marie-Christine Chartier-Harlin
Parkinson's disease (PD) is a progressive movement neurodegenerative disease associated with a loss of dopaminergic neurons in the substantia nigra of the brain. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, is thought to play an important role in dopaminergic neurotoxicity. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases are multi-subunit enzymatic complexes that generate reactive oxygen species as their primary function. Increased immunoreactivities for the NADPH oxidases catalytic subunits Nox1, Nox2 and Nox4 have been reported in the brain of PD patients...
November 13, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29130486/rtp801-is-a-critical-factor-in-the-neurodegeneration-process-of-a53t-alpha-synuclein-in-a-mouse-model-of-parkinson-s-disease-under-chronic-restraint-stress
#10
Zhao Zhang, Shi-Feng Chu, Sha-Sha Wang, Yi-Na Jiang, Yan Gao, Peng-Fei Yang, Qi-Di Ai, Nai-Hong Chen
BACKGROUND AND PURPOSE: The incidence of Parkinson's disease exhibited a younger tendency in recent years with the constantly increased stressors of modern society, but this relationship remains obscured. We performed this study to investigate whether stress contributes to this tendency and identify the executor during this process. EXPERIMENTAL APPROACH: Ten-month-old α-synuclein A53T mice, a PD mice model, were treated with chronic restraint stress (CRS) to simulate a PD-sensitive person with constant stress stimulation...
November 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29130469/-heparan-sulphates-amyloidosis-and-neurodegeneration
#11
REVIEW
C Vera, J A Alvarez-Orozco, A Maiza, S Chantepie, R N Chehin, M O Ouidja, D Papy-Garcia
INTRODUCTION: A number of neurodegenerative disorders have been linked directly to the accumulation of amyloid fibres. These fibres are made up of proteins or peptides with altered structures and which join together in vivo in association with heparan sulphate-type polysaccharides. AIMS: To examine the most recent concepts in the biology of heparan sulphates and their role in the aggregation of the peptide Abeta, of tau protein, of alpha-synuclein and of prions...
November 16, 2017: Revista de Neurologia
https://www.readbyqxmd.com/read/29129675/alpha-synuclein-dimerization-in-erythrocytes-of-patients-with-genetic-and-non-genetic-forms-of-parkinson-s-disease
#12
Nikolaos Papagiannakis, Christos Koros, Maria Stamelou, Athina-Maria Simitsi, Matina Maniati, Roubina Antonelou, Dimitra Papadimitriou, Georgia Dermentzaki, Marina Moraitou, Helen Michelakakis, Leonidas Stefanis
BACKGROUND: Variations of α-synuclein levels or species have been reported in Parkinson's Disease (PD). There has been little systematic examination of erythrocytes, a rich source of α-synuclein. METHODS: Erythrocyte membranes were obtained from PD patients (mutation carriers in the α-synuclein gene (A53T-PD) and glucocerebrosidase gene (GBA-PD) (n=18 each), and patients without known mutations (GU-PD, n=56)), and age-/sex-matched controls (n=56). Levels of monomeric and dimeric α-synuclein were assessed using Western immunoblotting...
November 9, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29124790/neuropathology-of-genetic-synucleinopathies-with-parkinsonism-review-of-the-literature
#13
REVIEW
Susanne A Schneider, Roy N Alcalay
Clinical-pathological studies remain the gold-standard for the diagnosis of Parkinson's disease (PD). However, mounting data from genetic PD autopsies challenge the diagnosis of PD based on Lewy body pathology. Most of the confirmed genetic risks for PD show heterogenous neuropathology, even within kindreds, which may or may not include Lewy body pathology. We review the literature of genetic PD autopsies from cases with molecularly confirmed PD or parkinsonism and summarize main findings on SNCA (n = 25), Parkin (n = 20, 17 bi-allelic and 3 heterozygotes), PINK1 (n = 5, 1 bi-allelic and 4 heterozygotes), DJ-1 (n = 1), LRRK2 (n = 55), GBA (n = 10 Gaucher disease patients with parkinsonism), DNAJC13, GCH1, ATP13A2, PLA2G6 (n = 8 patients, 2 with PD), MPAN (n = 2), FBXO7, RAB39B, and ATXN2 (SCA2), as well as on 22q deletion syndrome (n = 3)...
November 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29124503/urological-dysfunction-in-synucleinopathies-epidemiology-pathophysiology-and-management
#14
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/29123078/high-performance-liquid-chromatography-mass-spectrometry-lc-ms-based-quantitative-lipidomics-study-of-ganglioside-nana-3-plasma-to-establish-its-association-with-parkinson-s-disease-patients
#15
Jinzhi Zhang, Xiao Zhang, Lijuan Wang, Caidi Yang
BACKGROUND It is well known that, pathologically, Parkinson's disease is a common neurodegenerative disorder. In Parkinson's disease, the protein which is abundant in the human brain, alpha-synuclein, accumulates inside the nerve cells. In this situation, dysregulation of lipid metabolism performs a crucial role; however, its association with Parkinson's disease is has not yet been explored. MATERIAL AND METHODS We performed a high-performance liquid chromatography-mass spectrometry-derived quantitative lipidomics study to analyze the profile of lipidomic plasma obtained from 170 PD patients and 120 controls, taken from our hospital...
November 10, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29119326/neurodegeneration-and-the-ordered-assembly-of-%C3%AE-synuclein
#16
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/29118344/delivery-of-native-proteins-into-c-elegans-using-a-transduction-protocol-based-on-lipid-vesicles
#17
Michele Perni, Francesco A Aprile, Sam Casford, Benedetta Mannini, Pietro Sormanni, Christopher M Dobson, Michele Vendruscolo
The nematode worm Caenorhabditis elegans (C. elegans) is a versatile and widely used animal model for in vivo studies of a broad range of human diseases, in particular for understanding their genetic origins and for screening drug candidates. Nevertheless, the challenges associated with the administration of native proteins to C. elegans have limited the range of applications of this animal model in protein-based drug discovery programs. Here, we describe a readily usable protocol for the transduction of native proteins in C...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29116402/a-critical-review-of-the-prion-hypothesis-of-human-synucleinopathies
#18
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
#19
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/29115353/lysophosphatidylcholine-modulates-the-aggregation-of-human-islet-amyloid-polypeptide
#20
Yanting Xing, Emily H Pilkington, Miaoyi Wang, Cameron J Nowell, Aleksandr Kakinen, Yunxiang Sun, Bo Wang, Thomas P Davis, Feng Ding, Pu Chun Ke
Amyloid aggregation of human islet amyloid polypeptide (IAPP) is a hallmark of type 2 diabetes (T2D), a metabolic disease and a global epidemic. Although IAPP is synthesized in pancreatic β-cells, its fibrils and plaques are found in the extracellular space indicating a causative transmembrane process. Numerous biophysical studies have revealed that cell membranes as well as model lipid vesicles promote the aggregation of amyloid-β (associated with Alzheimer's), α-synuclein (associated with Parkinson's) and IAPP, through electrostatic and hydrophobic interactions between the proteins/peptides and lipid membranes...
November 8, 2017: Physical Chemistry Chemical Physics: PCCP
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