keyword
MENU ▼
Read by QxMD icon Read
search

synuclein and aggregation

keyword
https://www.readbyqxmd.com/read/29681846/high-dietary-iron-supplement-induces-the-nigrostriatal-dopaminergic-neurons-lesion-in-transgenic-mice-expressing-mutant-a53t-human-alpha-synuclein
#1
Fengju Jia, Ning Song, Weiwei Wang, Xixun Du, Yajing Chi, Hong Jiang
Both alpha-synuclein aggregation and iron deposits are neuropathological hallmarks of Parkinson's disease (PD). We are particularly interested in whether iron could synergize with alpha-synuclein pathology in vivo , especially in the nigrostriatal system. In the present study, we reported transgenic mice with overexpressing human A53T alpha-synuclein, as well as WT mice with high dietary iron displayed hyperactive motor coordination and impaired colonic motility, compared with those with basal dietary iron...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29681024/extracellular-alpha-synuclein-oligomers-induce-parkin-s-nitrosylation-relevance-to-sporadic-parkinson-s-disease-etiopathology
#2
Anna Wilkaniec, Anna M Lenkiewicz, Grzegorz A Czapski, Henryk M Jęśko, Wojciech Hilgier, Robert Brodzik, Magdalena Gąssowska-Dobrowolska, Carsten Culmsee, Agata Adamczyk
α-Synuclein (ASN) and parkin, a multifunctional E3 ubiquitin ligase, are two proteins that are associated with the pathophysiology of Parkinson's disease (PD). Excessive release of ASN, its oligomerization, aggregation, and deposition in the cytoplasm contribute to neuronal injury and cell death through oxidative-nitrosative stress induction, mitochondrial impairment, and synaptic dysfunction. In contrast, overexpression of parkin provides protection against cellular stresses and prevents dopaminergic neural cell loss in several animal models of PD...
April 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29679389/down-regulation-of-nramp1-is-associated-with-mptp-mpp-induced-%C3%AE-synuclein-accumulation-and-neurotoxicity
#3
Kuo-Chen Wu, Horng-Huei Liou, Chih-Yu Lee, Chun-Jung Lin
AIMS: The accumulation of α-synuclein is a hallmark in the pathogenesis of Parkinson's disease (PD). Natural resistance-associated macrophage protein-1 (Nramp1) was previously shown to contribute to the degradation of extracellular α-synuclein in microglia under conditions of iron overload. This study was aimed at investigating the role of Nramp1 in α-synuclein pathology in the neuron under MPTP/MPP+ treatment. METHODS: The expression of Nramp1 and pathological features (including iron and α-synuclein accumulation) were examined in the dopaminergic neurons of humans (with and without PD) and of mice (with and without receiving chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication)...
April 21, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29678776/comparison-of-the-3d-structures-of-mouse-and-human-%C3%AE-synuclein-fibrils-by-solid-state-nmr-and-stem
#4
Songhwan Hwang, Pascal Fricke, Maximilian Zinke, Karin Giller, Joseph S Wall, Dietmar Riedel, Stefan Becker, Adam Lange
Intra-neuronal aggregation of α-synuclein into fibrils is the molecular basis for α -synucleinopathies, such as Parkinson's disease. The atomic structure of human α -synuclein (hAS) fibrils was recently determined by Tuttle et al. using solid-state NMR (ssNMR). The previous study found that hAS fibrils are composed of a single protofilament. Here, we have investigated the structure of mouse α -synuclein (mAS) fibrils by STEM and isotope-dilution ssNMR experiments. We found that in contrast to hAS, mAS fibrils consist of two or even three protofilaments which are connected by rather weak interactions in between them...
April 17, 2018: Journal of Structural Biology
https://www.readbyqxmd.com/read/29676481/high-mobility-group-box-1-in-parkinson-s-disease-from-pathogenesis-to-therapeutic-approaches
#5
REVIEW
Efthalia Angelopoulou, Christina Piperi, Athanasios G Papavassiliou
Parkinson's disease (PD) presents the second most common neurodegenerative disorder with largely unknown pathogenesis and inefficient therapeutic management. Accumulating data indicate that neuroinflammation, autophagy impairment, α-synuclein aggregation and mitochondrial dysfunction may contribute to PD onset; however the molecular mechanisms underlying these pathophysiological processes are still under elucidation. Interestingly, recent evidence has indicated that High-mobility group box 1 (HMGB1), a DNA-binding protein that can be actively secreted by inflammatory cells and passively released by necrotic cells may play a key role in PD pathogenesis...
April 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29676021/detection-of-alpha-synuclein-conformational-variants-from-gastro-intestinal-biopsy-tissue-as-a-potential-biomarker-for-parkinson-s-disease
#6
Claudio Ruffmann, Nora Bengoa-Vergniory, Ilaria Poggiolini, Diane Ritchie, Michele T Hu, Javier Alegre-Abarrategui, Laura Parkkinen
AIMS: Gastrointestinal (GI) α-synuclein (aSyn) detection as a potential biomarker of Parkinson's disease (PD) is challenged by conflicting results of recent studies. To increase sensitivity and specificity, we applied three techniques to detect different conformations of aSyn in GI biopsies obtained from a longitudinal, clinically well-characterized cohort of PD patients and healthy controls (HC). METHODS: With immunohistochemistry (IHC), we used antibodies reactive for total, phosphorylated and oligomeric aSyn; with aSyn proximity ligation assay (AS-PLA), we targeted oligomeric aSyn species specifically; and with paraffin-embedded tissue blot (AS-PET-blot) we aimed to detect fibrillary, synaptic aSyn...
April 19, 2018: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/29673913/epothilone-d-inhibits-microglia-mediated-spread-of-alpha-synuclein-aggregates
#7
Dario Valdinocci, Gary Grant, Tracey Dickson, Dean L Pountney
Multiple System Atrophy (MSA) is a progressive neurodegenerative disease characterized by chronic neuroinflammation and widespread α-synuclein (α-syn) cytoplasmic inclusions. Neuroinflammation associated with microglial cells is typically located in brain regions with α-syn deposits. The potential link between microglial cell migration and the transport of pathological α-syn protein in MSA was investigated. Qualitative analysis via immunofluorescence of MSA cases (n = 4) revealed microglial cells bearing α-syn inclusions distal from oligodendrocytes bearing α-syn cytoplasmic inclusions, as well as close interactions between microglia and oligodendrocytes bearing α-syn, suggestive of a potential transfer mechanism between microglia and α-syn bearing cells in MSA and the possibility of microglia acting as a mobile vehicle to spread α-syn between anatomically connected brain regions...
April 16, 2018: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/29670081/seipin-deficiency-in-mice-causes-loss-of-dopaminergic-neurons-via-aggregation-and-phosphorylation-of-%C3%AE-synuclein-and-neuroinflammation
#8
Ling Wang, Juan Hong, Yajuan Wu, George Liu, Wenfeng Yu, Ling Chen
Seipin gene is originally found in type 2 congenital generalized lipodystrophy (CGL2) to involve lipid droplet formation. Recently, decrease of seipin expression is reported in substantia nigra of Parkinson's disease patients. Dopaminergic neurons in substantia nigra pars compacta expressed the seipin protein. The objective of this study is to investigate influence of the seipin deficiency on dopaminergic neurons and motor behaviors. Neuronal seipin knockout (seipin-nKO) mice (3-12 months of age) displayed an age-related deficit in motor coordination...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29669601/potent-prion-like-behaviors-of-pathogenic-%C3%AE-synuclein-and-evaluation-of-inactivation-methods
#9
Airi Tarutani, Tetsuaki Arai, Shigeo Murayama, Shin-Ichi Hisanaga, Masato Hasegawa
The concept that abnormal protein aggregates show prion-like propagation between cells has been considered to explain the onset and progression of many neurodegenerative diseases. Indeed, both synthetic amyloid-like fibrils and pathogenic proteins extracted from patients' brains induce self-templated amplification and cell-to-cell transmission in vitro and in vivo. However, it is unclear whether exposure to exogenous prion-like proteins can potentially cause these diseases in humans. Here, we investigated in detail the prion-like seeding activities of several kinds of pathogenic α-synuclein (α-syn), including synthetic fibrils and detergent-insoluble fractions extracted from brains of patients with α-synucleinopathies...
April 18, 2018: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/29669468/inducible-alpha-synuclein-expression-affects-human-neural-stem-cell-behavior
#10
Jacopo Zasso, Ahmed Mastad, Alessandro Cutarelli, Luciano Conti
Converging evidence suggest that levels of alpha-Synuclein (aSyn) expression play a critical role in Parkinson's disease (PD). Several mutations of the SNCA gene, encoding for aSyn have been associated to either the familial or the sporadic forms of PD. Nonetheless, the mechanism underlying wild type aSyn-mediated neurotoxicity in neuronal cells as well as its specific driving role in PD pathogenesis has yet to be fully clarified. In this view, the development of proper in vitro cellular systems is a crucial step...
April 19, 2018: Stem Cells and Development
https://www.readbyqxmd.com/read/29663556/structure-and-dynamics-of-the-extended-helix-state-of-alpha-synuclein-intrinsic-lability-of-the-linker-region
#11
Yoon-Hui Sung, David Eliezer
The Parkinson's protein alpha-synuclein binds to synaptic vesicles in vivo and adopts a highly extended helical conformation when binding to lipid vesicles in vitro. High-resolution structural analysis of alpha-synuclein bound to small lipid or detergent micelles revealed two helices connected by a non-helical linker, but corresponding studies of the vesicle-bound extended-helix state are hampered by the size and heterogeneity of the protein-vesicle complex. Here we employ fluorinated alcohols (FAs) to induce a highly helical aggregation-resistant state of alpha-synuclein in solution that resembles the vesicle-bound extended-helix state but is amenable to characterization using high-resolution solution-state NMR...
April 16, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29662651/p27-kip1-regulates-alpha-synuclein-expression
#12
Edurne Gallastegui, Carla Domuro, Joan Serratosa, Alejandra Larrieux, Laura Sin, Jonatan Martinez, Arnaud Besson, José Manuel Morante-Redolat, Serena Orlando, Rosa Aligue, Isabel Fariñas, María Jesús Pujol, Oriol Bachs
Alpha-synuclein (α-SYN) is the main component of anomalous protein aggregates (Lewy bodies) that play a crucial role in several neurodegenerative diseases (synucleinopathies) like Parkinson's disease and multiple system atrophy. However, the mechanisms involved in its transcriptional regulation are poorly understood. We investigated here the role of the cyclin-dependent kinase (Cdk) inhibitor and transcriptional regulator p27Kip1 (p27) in the regulation of α-SYN expression. We observed that selective deletion of p27 by CRISPR/Cas9 technology in neural cells resulted in increased levels of α-SYN...
March 27, 2018: Oncotarget
https://www.readbyqxmd.com/read/29656363/2-pentadecyl-2-oxazoline-reduces-neuroinflammatory-environment-in-the-mptp-model-of-parkinson-disease
#13
Marika Cordaro, Rosalba Siracusa, Rosalia Crupi, Daniela Impellizzeri, Alessio Filippo Peritore, Ramona D'Amico, Enrico Gugliandolo, Rosanna Di Paola, Salvatore Cuzzocrea
Current pharmacological management of Parkinson disease (PD) does not provide for disease modification, but addresses only symptomatic features. Here, we explore a new approach to neuroprotection based on the use of 2-pentadecyl-2-oxazoline (PEA-OXA), the oxazoline derivative of the fatty acid amide signaling molecule palmitoylethanolamide (PEA), in an experimental model of PD. Daily oral treatment with PEA-OXA (10 mg/kg) significantly reduced behavioral impairments and neuronal cell degeneration of the dopaminergic tract induced by four intraperitoneal injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on 8-week-old male C57 mice...
April 14, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29655942/pink1-p-k520rfsx3-mutation-identified-in-a-chinese-family-with-early-onset-parkinson-s-disease
#14
Peng Wang, Yi Guo, Chengyuan Song, Yiming Liu, Hao Deng
Parkinson's disease (PD) features selective loss of dopaminergic neurons of the substantia nigra pars compacta accompanied by the accumulation and aggregation of alpha-synuclein in Lewy bodies. PTEN induced putative kinase 1 gene (PINK1) mutations are the second most common genetic cause of autosomal recessive early-onset Parkinson's disease (EOPD). A single nucleotide deletion in PINK1 exon 8 (c.1557delG) was identified in a consanguineous Chinese family with EOPD. The homozygous deletion was co-segregated with disease in the family and resulted in a frameshift after codon 520 with a premature termination at codon 522 (p...
April 12, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29650757/conformational-flexibility-within-the-nascent-polypeptide-associated-complex-enables-its-interactions-with-structurally-diverse-client-proteins
#15
Esther M Martin, Matthew P Jackson, Martin Gamerdinger, Karina Gense, Theodoros K Karamanos, Julia R Humes, Elke Deuerling, Alison E Ashcroft, Sheena E Radford
As newly synthesized polypeptides emerge from the ribosome, it is crucial that they fold correctly. To prevent premature aggregation, nascent chains interact with chaperones that facilitate folding or prevent misfolding until protein synthesis is complete. Nascent polypeptide-associated complex (NAC) is a ribosome-associated chaperone important for protein homeostasis. However, how NAC binds its substrates remains unclear. Using native electrospray ionization MS (ESI MS), limited proteolysis, NMR and cross-linking, we analysed the conformational properties of NAC from Caenorhabditis elegans and studied its ability to bind proteins in different conformational states...
April 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29649746/degradation-of-alpha-synuclein-by-dendritic-cell-factor-1-delays-neurodegeneration-and-extends-lifespan-in-drosophila
#16
Shiqing Zhang, Ruili Feng, Yanhui Li, Linhua Gan, Fangfang Zhou, Shiquan Meng, Qian Li, Tieqiao Wen
Parkinson's disease (PD) is a common neurodegenerative disease associated with the progressive loss of dopaminergic neurons in the substantia nigra. Proteinaceous depositions of alpha-synuclein (α-syn) and its mutations, A30P and A53T, are one important characteristic of PD. However, little is known about their aggregation and degradation mechanisms. Dendritic cell factor 1 (DCF1) is a membrane protein that plays important roles in nerve development in mouse. In this study, we aimed to show that DCF1 overexpression in a PD Drosophila model significantly ameliorates impaired locomotor behavior in third instar larvae and normalizes neuromuscular junction growth...
March 13, 2018: Neurobiology of Aging
https://www.readbyqxmd.com/read/29625255/genetic-enhancement-of-macroautophagy-in-vertebrate-models-of-neurodegenerative-diseases
#17
REVIEW
Patrick Ejlerskov, Avraham Ashkenazi, David C Rubinsztein
Most of the neurodegenerative diseases that afflict humans manifest with the intraneuronal accumulation of toxic proteins which are aggregate-prone. Extensive data in cell and neuronal models support the concept that such proteins, like mutant huntingtin or alpha-synuclein, are substrates for macroautophagy (hereafter autophagy). Furthermore, autophagy-inducing compounds lower the levels of such proteins and ameliorate their toxicity in diverse animal models of neurodegenerative diseases. However, most of these compounds also have autophagy-independent effects and it is important to understand if similar benefits are seen with genetic strategies that upregulate autophagy, as this strengthens the validity of this strategy in such disease...
April 3, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29624752/biomarkers-for-cognitive-impairment-in-lewy-body-disorders-status-and-relevance-for-clinical-trials
#18
REVIEW
Andrew Siderowf, Dag Aarsland, Brit Mollenhauer, Jennifer G Goldman, Bernard Ravina
Biomarkers have the potential to improve diagnosis and prognosis, and guide clinical treatment decisions. In research, biomarkers can be used for patient selection and as outcome measures in clinical trials. A range of biochemical and imaging biomarkers are relevant to patients with Lewy body disorders, including PD, PD dementia, and dementia with Lewy bodies. Dopaminergic imaging is used for differential diagnosis of parkinsonian disorders versus tremor disorders without dopamingeric deficits, and also to differentiate dementia with Lewy bodies from Alzheimer's disease...
April 2018: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/29624735/cx3cr1-deficiency-exacerbates-alpha-synuclein-a53t-induced-neuroinflammation-and-neurodegeneration-in-a-mouse-model-of-parkinson-s-disease
#19
Sara Castro-Sánchez, Ángel J García-Yagüe, Tresa López-Royo, Maria Casarejos, José Luis Lanciego, Isabel Lastres-Becker
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the substantia nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant is alpha-synuclein (α-SYN). Mutations of the gene that codes for α-SYN (SNCA), such as the A53T mutation, and duplications of the gene generate cases of PD with autosomal dominant inheritance. As a result of the association of inflammation with the neurodegeneration of PD, we analyzed whether overexpression of wild-type α-SYN (α-SYNWT ) or mutated α-SYN (α-SYNA53T ) are involved in the neuronal dopaminergic loss and inflammation process, along with the role of the chemokine fractalkine (CX3CL1) and its receptor (CX3CR1)...
April 6, 2018: Glia
https://www.readbyqxmd.com/read/29623065/-in-situ-proximity-ligation-assay-reveals-co-localization-of-alpha-synuclein-and-snare-proteins-in-murine-primary-neurons
#20
Leire Almandoz-Gil, Emma Persson, Veronica Lindström, Martin Ingelsson, Anna Erlandsson, Joakim Bergström
The aggregation of alpha-synuclein (αSyn) is the pathological hallmark of Parkinson's disease, dementia with Lewy bodies and related neurological disorders. However, the physiological function of the protein and how this function relates to its pathological effects remain poorly understood. One of the proposed roles of αSyn is to promote the soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex assembly by binding to VAMP-2. The objective of this study was to visualize the co-localization between αSyn and the SNARE proteins (VAMP-2, SNAP-25, and syntaxin-1) for the first time using in situ proximity ligation assay (PLA)...
2018: Frontiers in Neurology
keyword
keyword
105426
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"