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https://www.readbyqxmd.com/read/29151169/parkinson-s-disease-experimental-models-and-reality
#1
REVIEW
Peizhou Jiang, Dennis W Dickson
Parkinson's disease (PD) is a chronic, progressive movement disorder of adults and the second most common neurodegenerative disease after Alzheimer's disease. Neuropathologic diagnosis of PD requires moderate-to-marked neuronal loss in the ventrolateral substantia nigra pars compacta and α-synuclein (αS) Lewy body pathology. Nigrostriatal dopaminergic neurodegeneration correlates with the Parkinsonian motor features, but involvement of other peripheral and central nervous system regions leads to a wide range of non-motor features...
November 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29151060/genetics-of-parkinson-s-disease-and-related-disorders
#2
REVIEW
Pei-Lan Zhang, Yan Chen, Chen-Hao Zhang, Yu-Xin Wang, Pedro Fernandez-Funez
Parkinson's disease (PD) is a complex and heterogeneous neurological condition characterised mainly by bradykinesia, resting tremor, rigidity and postural instability, symptoms that together comprise the parkinsonian syndrome. Non-motor symptoms preceding and following clinical onset are also helpful diagnostic markers revealing a widespread and progressive pathology. Many other neurological conditions also include parkinsonism as primary or secondary symptom, confounding their diagnosis and treatment. Although overall disease course and end-stage pathological examination single out these conditions, the significant overlaps suggest that they are part of a continuous disease spectrum...
November 18, 2017: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29150919/a-focus-on-the-beneficial-effects-of-alpha-synuclein-and-a-re-appraisal-of-synucleinopathies
#3
Larisa Ryskalin, Carla L Busceti, Fiona Limanaqi, Francesca Biagioni, Stefano Gambardella, Francesco Fornai
Alpha synuclein (α-syn) belongs to a class of proteins which are commonly considered to play a detrimental role in neuronal survival. This assumption is based on the occurrence of a severe neuronal degeneration in patients carrying a multiplication of the α-syn gene (SNCA) and in a variety of experimental models, where overexpression of α-syn leads to cell death and neurological impairment. In these conditions, a higher amount of normally structured α-syn produces a damage, which is even worse compared with that produced by α-syn owing an abnormal structure (as occurring following point gene mutations)...
November 16, 2017: Current Protein & Peptide Science
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
#4
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/29149481/neuroprotective-effects-of-melatonin-on-amphetamine-induced-dopaminergic-fiber-degeneration-in-the-hippocampus-of-postnatal-rats
#5
Tanawan Leeboonngam, Ratchadaporn Pramong, Kwankanit Sae-Ung, Piyarat Govitrapong, Pansiri Phansuwan-Pujito
Chronic amphetamine (AMPH) abuse leads to damage of the hippocampus, the brain area associated with learning and memory process. Previous results have shown that AMPH-induced dopamine neurotransmitter release, reactive oxygen species formation and degenerative protein aggregation lead to neuronal death. Melatonin, a powerful antioxidant, plays a role as a neuroprotective agent. The objective of this study was to investigate whether the protective effect of melatonin on AMPH-induced hippocampal damage in the postnatal rat acts through the dopaminergic pathway...
November 17, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/29149290/discovering-the-3-utr-mediated-regulation-of-alpha-synuclein
#6
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
#7
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/29147557/the-diversity-and-utility-of-amyloid-fibrils-formed-by-short-amyloidogenic-peptides
#8
REVIEW
Zahraa S Al-Garawi, Kyle L Morris, Karen E Marshall, Jutta Eichler, Louise C Serpell
Amyloidogenic peptides are well known for their involvement in diseases such as type 2 diabetes and Alzheimer's disease. However, more recently, amyloid fibrils have been shown to provide scaffolding and protection as functional materials in a range of organisms from bacteria to humans. These roles highlight the incredible tensile strength of the cross-β amyloid architecture. Many amino acid sequences are able to self-assemble to form amyloid with a cross-β core. Here we describe our recent advances in understanding how sequence contributes to amyloidogenicity and structure...
December 6, 2017: Interface Focus
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
#9
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
#10
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/29142509/using-an-nmr-metabolomics-approach-to-investigate-the-pathogenicity-of-amyloid-beta-and-alpha-synuclein
#11
M M Phelan, E Caamaño-Gutiérrez, M S Gant, R X Grosman, J Madine
Introduction: The pathogenicity at differing points along the aggregation pathway of many fibril-forming proteins associated with neurodegenerative diseases is unclear. Understanding the effect of different aggregation states of these proteins on cellular processes is essential to enhance understanding of diseases and provide future options for diagnosis and therapeutic intervention. Objectives: To establish a robust method to probe the metabolic changes of neuronal cells and use it to monitor cellular response to challenge with three amyloidogenic proteins associated with neurodegenerative diseases in different aggregation states...
2017: Metabolomics: Official Journal of the Metabolomic Society
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
#12
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
#13
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
#14
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
#15
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/29134321/co-occurrence-of-mixed-proteinopathies-in-late-stage-huntington-s-disease
#16
Isabelle St-Amour, Andréanne Turgeon, Claudia Goupil, Emmanuel Planel, Sébastien S Hébert
Accumulating evidence highlights the potential role of mixed proteinopathies (i.e., abnormal protein aggregation) in the development of clinical manifestations of neurodegenerative diseases (NDD). Huntington's disease (HD) is an inherited NDD caused by autosomal-dominant expanded CAG trinucleotide repeat mutation in the gene coding for Huntingtin (Htt). Previous studies have suggested the coexistence of phosphorylated-Tau, α-synuclein (α-Syn) and TAR DNA-binding protein 43 (TDP-43) inclusions in HD. However, definite evidence that HD pathology in humans can be accompanied by other proteinopathies is still lacking...
November 13, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/29132391/nadph-oxidases-in-parkinson-s-disease-a-systematic-review
#17
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
#18
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
#19
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
#20
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
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