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alpha synuclein and aggregation

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https://www.readbyqxmd.com/read/29143358/melatonin-improves-survival-and-respiratory-activity-of-yeast-cells-challenged-by-alpha-synuclein-and-menadione
#1
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
#2
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/29137980/interaction-of-alpha-synuclein-with-cytogaligin-a-protein-encoded-by-the-proapoptotic-gene-galig
#3
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/29130469/-heparan-sulphates-amyloidosis-and-neurodegeneration
#4
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/29124503/urological-dysfunction-in-synucleinopathies-epidemiology-pathophysiology-and-management
#5
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/29107086/age-dependent-elevations-of-oligomeric-and-phosphorylated-alpha-synuclein-synchronously-occurs-in-the-brain-and-gastrointestinal-tract-of-cynomolgus-monkeys
#6
Xin Li, Weiwei Yang, Xuran Li, Min Chen, Chengwei Liu, Shun Yu
Fibrillary α-synuclein (α-syn), which constitutes the major component of Lewy pathology characterized for Parkinson's disease (PD), is found also in the aged enteric nervous system (ENS) and central nervous system (CNS). However, what happens to oligomeric α-syn (o-α-syn) in the aged ENS and CNS remains poorly understood. Here, by using ELISA methods specific for o-α-syn and phosphorylated α-syn (p-α-syn), we measured the levels of o-α-syn and p-α-syn in the gastrointestinal (GI) tract and brain of aging cynomolgus monkeys...
October 26, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/29089869/microrna-101-modulates-autophagy-and-oligodendroglial-alpha-synuclein-accumulation-in-multiple-system-atrophy
#7
Elvira Valera, Brian Spencer, Jennifer Mott, Margarita Trejo, Anthony Adame, Michael Mante, Edward Rockenstein, Juan C Troncoso, Thomas G Beach, Eliezer Masliah, Paula Desplats
Synucleinopathies, neurodegenerative disorders with alpha-synuclein (α-syn) accumulation, are the second leading cause of neurodegeneration in the elderly, however no effective disease-modifying alternatives exist for these diseases. Multiple system atrophy (MSA) is a fatal synucleinopathy characterized by the accumulation of toxic aggregates of α-syn within oligodendroglial cells, leading to demyelination and neurodegeneration, and the reduction of this accumulation might halt the fast progression of MSA...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29089438/human-astrocytes-transfer-aggregated-alpha-synuclein-via-tunneling-nanotubes
#8
Jinar Rostami, Staffan Holmqvist, Veronica Lindström, Jessica Sigvardson, Gunilla T Westermark, Martin Ingelsson, Joakim Bergström, Laurent Roybon, Anna Erlandsson
Many lines of evidence suggest that the Parkinson's disease (PD) related protein alpha-synuclein (α-SYN) can propagate from cell-to-cell in a prion-like manner. However, the cellular mechanisms behind the spreading remain elusive. Here, we show that human astrocytes, derived from embryonic stem cells, actively transfer aggregated α-SYN to nearby astrocytes via direct contact and tunneling nanotubes (TNTs). Failure in the astrocytes' lysosomal digestion of excess α-SYN oligomers, results in α-SYN deposits in the trans-Golgi network followed by endoplasmic reticulum swelling and mitochondrial disturbances...
October 31, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29069955/shatavarin-iv-elicits-lifespan-extension-and-alleviates-parkinsonism-in-caenorhabditis-elegans
#9
Shachi Shuchi Smita, Shreesh Raj Sammi, Tulsankar S Laxman, Rabi S Bhatta, Rakesh Pandey
Shatavarin IV (SIV), a steroidal saponin is a major bioactive phytomolecule present in roots of Asparagus racemosus (Liliaceae) known for its anticancer activity. Age associated neurodegenerative Parkinson's disease (PD) is characterized by alpha-synuclein aggregation in dopaminergic neuron resulting in neurodegeneration. The invention of bioactive molecules that delay aging and age associated disorders endorses development of natural phytomolecule as a therapeutic agent for curing age related diseases. Therefore, present study for the first time explores the potential of SIV against aging and Parkinsonism utilizing Caenorhabditis elegans model system...
October 25, 2017: Free Radical Research
https://www.readbyqxmd.com/read/29064068/dexamethasone-inhibits-copper-induced-alpha-synuclein-aggregation-by-a-metallothionein-dependent-mechanism
#10
Fleur A McLeary, Alexandre N Rcom-H'cheo-Gauthier, Jessica Kinder, Michael Goulding, Tien K Khoo, George D Mellick, Roger S Chung, Dean L Pountney
Intracellular aggregates of α-synuclein are the pathological hallmark of Parkinson's disease (PD) and dementia with Lewy bodies (DLB), being linked to neurotoxicity. Multiple triggers of α-synuclein aggregation have been implicated, including raised copper. The potential protective role of the endogenous copper-/zinc-binding proteins, metallothioneins (MT), has been explored in relation to copper-induced α-synuclein aggregation. Up-regulated endogenous expression of MT was induced in SHSY-5Y cells by the synthetic glucocorticoid analogue, dexamethasone...
October 24, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/29021741/the-neuroprotective-role-of-protein-quality-control-in-halting-the-development-of-alpha-synuclein-pathology
#11
REVIEW
Destiny-Love Manecka, Benoît Vanderperre, Edward A Fon, Thomas M Durcan
Synucleinopathies are a family of neurodegenerative disorders that comprises Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Each of these disorders is characterized by devastating motor, cognitive, and autonomic consequences. Current treatments for synucleinopathies are not curative and are limited to improvement of quality of life for affected individuals. Although the underlying causes of these diseases are unknown, a shared pathological hallmark is the presence of proteinaceous inclusions containing the α-synuclein (α-syn) protein in brain tissue...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28987463/therapeutic-approaches-to-target-alpha-synuclein-pathology
#12
REVIEW
Patrik Brundin, Kuldip D Dave, Jeffrey H Kordower
Starting two decades ago with the discoveries of genetic links between alpha-synuclein and Parkinson's disease risk and the identification of aggregated alpha-synuclein as the main protein constituent of Lewy pathology, alpha-synuclein has emerged as the major therapeutic target in Parkinson's disease and related synucleinopathies. Following the suggestion that alpha-synuclein pathology gradually spreads through the nervous system following a stereotypic pattern and the discovery that aggregated forms of alpha-synuclein can propagate pathology from one cell to another, and thereby probably aggravate existing deficits as well as generate additional symptoms, the idea that alpha-synuclein is a viable therapeutic target gained further support...
October 4, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28981090/is-trehalose-an-autophagic-inducer-unraveling-the-roles-of-non-reducing-disaccharides-on-autophagic-flux-and-alpha-synuclein-aggregation
#13
Ye-Seul Yoon, Eun-Duk Cho, Woo Jung Ahn, Kyung Won Lee, Seung-Jae Lee, He-Jin Lee
Autophagy is a pivotal intracellular process by which cellular macromolecules are degraded upon various stimuli. A failure in the degradation of autophagic substrates such as impaired organelles and protein aggregates leads to their accumulations, which are characteristics of many neurodegenerative diseases. Pharmacological activation of autophagy has thus been considered a prospective therapeutic approach for treating neurodegenerative diseases. Among a number of autophagy-inducing agents, trehalose has received attention for its beneficial effects in different disease models of neurodegeneration...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28968082/c-terminal-truncated-%C3%AE-synuclein-fibrils-contain-strongly-twisted-%C3%AE-sheets
#14
Aditya Iyer, Steven J Roeters, Vladimir Kogan, Sander Woutersen, Mireille M A E Claessens, Vinod Subramaniam
C-terminal truncations of monomeric wild-type alpha-synuclein (henceforth WT-αS) have been shown to enhance the formation of amyloid aggregates both in vivo and in vitro and have been associated with accelerated progression of Parkinson's disease (PD). The correlation with PD may not solely be a result of faster aggregation, but also of which fibril polymorphs are preferentially formed when the C-terminal residues are deleted. Considering that different polymorphs are known to result in distinct pathologies, it is important to understand how these truncations affect the organization of αS into fibrils...
November 1, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28957336/a-study-on-the-modulation-of-alpha-synuclein-fibrillation-by-scutellaria-pinnatifida-extracts-and-its-neuroprotective-properties
#15
Mahdyeh Sashourpour, Saber Zahri, Tayebeh Radjabian, Viktoria Ruf, Francisco Pan-Montojo, Dina Morshedi
Aggregation of alpha-synuclein (α-SN) is a key pathogenic event in Parkinson's disease (PD) leading to dopaminergic degeneration. The identification of natural compounds inhibiting α-SN aggregation may have a major role in treating PD. Different Scutellaria species are known as valuable medicinal plants, primarily due to their high flavonoid levels. Scutellaria pinnatifida (S. pinnatifida) is endemic to Iran; however, the knowledge of its pharmaceutical properties is limited. Here we report that S. pinnatifida extracts have an anti-fibrillation effect on α-SN aggregation and neuroprotective properties on PC12 and primary dopaminergic neurons...
2017: PloS One
https://www.readbyqxmd.com/read/28951838/alteration-in-biochemical-parameters-in-the-brain-of-transgenic-drosophila-melanogaster-model-of-parkinson-s-disease-exposed-to-apigenin
#16
Yasir Hasan Siddique, Smita Jyoti
BACKGROUND: Oxidative stress is one of the key components of the pathology of various neurodegenerative disorders. Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons owing to the aggregation of alpha-synuclein (αS) in the brain. A number of polyphenols have been reported to inhibit the αS aggregation resulting in the possible prevention of PD. The involvement of free radicals in mediating the neuronal death in PD has also been implicated. METHODS: In the present study, the transgenic flies expressing human αS in the brain were exposed to 10 μM, 20 μM, 40 μM, and 80 μM of apigenin established in diet for 24 days...
September 2017: Integrative medicine research
https://www.readbyqxmd.com/read/28948653/molecular-mechanisms-of-the-co-deposition-of-multiple-pathological-proteins-in-neurodegenerative-diseases
#17
Takashi Nonaka, Masami Masuda-Suzukake, Masato Hasegawa
Intracellular inclusions composed of abnormal protein aggregates are one of the neuropathological features of neurodegenerative diseases, and the formation of intracellular aggregates is believed to be associated with neurodegeneration leading to the onset of these diseases. In typical or pure cases, characteristic pathologies with one particular protein, such as tau, alpha-synuclein or trans-activation response DNA protein 43 (TDP-43), can be observed in brains of patients. On the other hand, multiple protein pathologies co-exist in many cases, raising the possibility that they may influence each other reciprocally in the pathogenesis and progression of the diseases...
September 25, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28933595/phosphoproteome-based-kinase-activity-profiling-reveals-the-critical-role-of-map2k2-and-plk1-in-neuronal-autophagy
#18
Lei-Lei Chen, Yong-Bo Wang, Ju-Xian Song, Wan-Kun Deng, Jia-Hong Lu, Li-Li Ma, Chuan-Bin Yang, Min Li, Yu Xue
Recent studies have demonstrated that dysregulation of macroautophagy/autophagy may play a central role in the pathogenesis of neurodegenerative disorders, and the induction of autophagy protects against the toxic insults of aggregate-prone proteins by enhancing their clearance. Thus, autophagy has become a promising therapeutic target against neurodegenerative diseases. In this study, quantitative phosphoproteomic profiling together with a computational analysis was performed to delineate the phosphorylation signaling networks regulated by 2 natural neuroprotective autophagy enhancers, corynoxine (Cory) and corynoxine B (Cory B)...
September 21, 2017: Autophagy
https://www.readbyqxmd.com/read/28927576/loss-of-microrna-7-regulation-leads-to-%C3%AE-synuclein-accumulation-and-dopaminergic-neuronal-loss-in%C3%A2-vivo
#19
Kirsty J McMillan, Tracey K Murray, Nora Bengoa-Vergniory, Oscar Cordero-Llana, Jane Cooper, Amy Buckley, Richard Wade-Martins, James B Uney, Michael J O'Neill, Liang F Wong, Maeve A Caldwell
Abnormal alpha-synuclein (α-synuclein) expression and aggregation is a key characteristic of Parkinson's disease (PD). However, the exact mechanism(s) linking α-synuclein to the other central feature of PD, dopaminergic neuron loss, remains unclear. Therefore, improved cell and in vivo models are needed to investigate the role of α-synuclein in dopaminergic neuron loss. MicroRNA-7 (miR-7) regulates α-synuclein expression by binding to the 3' UTR of the Synuclein Alpha Non A4 Component of Amyloid Precursor (SNCA) gene and inhibiting its translation...
October 4, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28924920/age-dependent-alpha-synuclein-accumulation-and-phosphorylation-in-the-enteric-nervous-system-in-a-transgenic-mouse-model-of-parkinson-s-disease
#20
Chong-Bin Zhong, Qian-Qian Chen, Caroline Haikal, Wen Li, Alexander Svanbergsson, Meike Diepenbroek, Jia-Yi Li
The enteric nervous system (ENS) controls the function of the gastrointestinal tract and has been implicated in various diseases, including Parkinson's disease (PD). PD is a neurodegenerative disease with Lewy bodies (LBs) and Lewy neurites (LNs) as the main pathological features. In addition to the typical motor symptoms in PD, attention has been drawn to non-motor symptoms, such as constipation, implying dysfunction of the ENS. In the present study, we characterized the age-dependent morphological alterations and aggregation of α-synuclein (α-syn), the primary protein component in LBs and LNs, in the ENS in an α-syn transgenic mouse model...
October 2017: Neuroscience Bulletin
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