Browse
Submit Data
Databases
API
Help

Dataset Information

4 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CryoEM dataset of sarkosyl-insoluble fractions from the putamen of multiple system atrophy brain of case 2

ABSTRACT:

SUBMITTER: Yang Shi

PROVIDER: EMPIAR-10358 | biostudies-other |

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Publications

Structures of α-synuclein filaments from multiple system atrophy.

Schweighauser Manuel M Shi Yang Y Tarutani Airi A Kametani Fuyuki F Murzin Alexey G AG Ghetti Bernardino B Matsubara Tomoyasu T Tomita Taisuke T Ando Takashi T Hasegawa Kazuko K Murayama Shigeo S Yoshida Mari M Hasegawa Masato M Scheres Sjors H W SHW Goedert Michel M

Nature 20200527 7825

Synucleinopathies, which include multiple system atrophy (MSA), Parkinson's disease, Parkinson's disease with dementia and dementia with Lewy bodies (DLB), are human neurodegenerative diseases<sup>1</sup>. Existing treatments are at best symptomatic. These diseases are characterized by the presence of, and believed to be caused by the formation of, filamentous inclusions of α-synuclein in brain cells<sup>2,3</sup>. However, the structures of α-synuclein filaments from the human brain are unknown ...[more]

PMID: 32461689

Similar Datasets

CryoEM dataset of sarkosyl-insoluble fractions from the putamen of multiple system atrophy brain of case 1

Project description: Not available

| EMPIAR-10357 | biostudies-other

RNA-seq in putamen of Multiple system atrophy patients

Project description:We performed RNA-seq on total RNA from tissue samples from putamen of the brain from Multiple system atrophy patients.

2020-02-01 | GSE134472 | GEO

Analysis of the sarkosyl-insoluble proteomes of Parkinson’s disease and Multiple System Atrophy subject brain samples

Project description:Aggregated alpha-synuclein (α-syn) is a principal constituent of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) that are observed respectively inside neurons in Parkinson’s disease (PD) and oligodendrocytes in multiple system atrophy (MSA). Yet, the cellular origin, the exact pathophysiological role, and the mechanism of formation of these inclusions remain to be elucidated. It has recently been proposed that pathological α-syn inclusions are capable of eventually causing the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or TDP-43 has also been put forward. The objective of this study was to examine the composition of these inclusions to gain insight into their origin and mechanisms of formation. We submitted sarkosyl-insoluble extracts of post-mortem brain tissue from PD and MSA patients and control subjects to a comparative proteomic analysis to address these points.

2022-02-17 | PXD024998 | Pride

Analysis of the total and sarkosyl-insoluble proteomes of controls, Parkinson’s disease and multiple system atrophy subject brain samples

Project description:Aggregated alpha-synuclein (α-syn) is a principal constituent of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) that are observed respectively inside neurons in Parkinson’s disease (PD) and oligodendrocytes in multiple system atrophy (MSA). Yet, the cellular origin, the exact pathophysiological role, and the mechanism of formation of these inclusions remain to be elucidated. It has recently been proposed that pathological α-syn inclusions are capable of eventually causing the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or TDP-43 has also been put forward. The objective of this study was to examine the composition of these inclusions to gain insight into their origin and mechanisms of formation. We submitted total solubilized and sarkosyl-insoluble extracts of post-mortem brain tissue from PD and MSA patients and control subjects to a comparative proteomic analysis to address these points. In parallel, we used proteomics for α-syn quantification in total solubilized brain homogenates and the respective sarkosyl-insoluble pellets as an unbiased validation of our results obtained by immunoblotting of these samples and fractions.

2024-03-25 | PXD039575 | Pride

RNA-seq in putamen of Multiple system atrophy patients

Project description:RNA-seq in putamen of Multiple system atrophy patients

| PRJNA555211 | ENA

Quantitative Validation of a Visual Rating Scale for Defining High-Iron Putamen in Patients With Multiple System Atrophy.

Project description:Objectives: To validate a visual rating scale reflecting sub-regional patterns of putaminal hypointensity in susceptibility-weighted imaging of patients with multiple system atrophy (MSA). Methods: Using a visual rating scale (from G0 to G3), 2 examiners independently rated putaminal hypointensities of 37 MSA patients and 21 control subjects. To investigate the correlation with the scales, R2* values and the volume of the entire putamen were measured. Results: MSA patients with parkinsonian variant had significantly higher scores than those with cerebellar variant. Visual rating scores in MSA were correlated with R2* values [General estimating equation (GEE), Wald chi-square = 25.89, corrected p < 0.001] and volume (Wald chi-square = 75.44, corrected p < 0.001). They correlated with UPDRS motor scores. Binary logistic regression analyses revealed that the visual rating scale was a significant predictor for discriminating MSA patients from controls [multivariate model adjusted for age and sex, odds ratio 52.722 (corrected p = 0.009)]. Pairwise comparison between areas under the curve (AUCs) revealed that the visual rating scale demonstrated higher accuracy than R2* values [difference between AUCs; univariate model = 0.247 (corrected p < 0.001); multivariate model = 0.186 (corrected p = 0.003)]. There were no significant differences in clinical characteristics between the high-iron group, defined as putamen with visual rating scale ≥ G2 and R2* values ≥ third quartile, and the remaining patients. Conclusion: The visual rating scale, which reflects quantitative iron content and atrophy of the putamen as well as motor severities, could be useful for the discrimination and evaluation of patients with MSA.

| S-EPMC6763953 | biostudies-literature

Proteome analysis of human nuclear insoluble fractions.

Project description:The interphase nucleus is a highly ordered and compartmentalized organelle. Little is known regarding what elaborate mechanisms might exist to explain these properties of the nucleus. Also unresolved is whether some architectural components might facilitate the formation of functional intranuclear compartments or higher order chromatin structure. As the first step to address these questions, we performed an in-depth proteome analysis of nuclear insoluble fractions of human HeLa-S3 cells prepared by two different approaches: a high-salt/detergent/nuclease-resistant fraction and a lithium 3,5-diiodosalicylate/nuclease-resistant fraction. Proteins of the fractions were analyzed by liquid chromatography electrospray ionization tandem mass spectrometry, identifying 333 and 330 proteins from each fraction respectively. Among the insoluble nuclear proteins, we identified 37 hitherto unknown or functionally uncharacterized proteins. The RNA recognition motif, WD40 repeats, HEAT repeats and the SAP domain were often found in these identified proteins. The subcellular distribution of selected proteins, including DEK protein and SON protein, demonstrated their novel associations with nuclear insoluble materials, corroborating our MS-based analysis. This study establishes a comprehensive catalog of the nuclear insoluble proteins in human cells. Further functional analysis of the proteins identified in our study will significantly improve our understanding of the dynamic organization of the interphase nucleus.

| S-EPMC4158948 | biostudies-literature

Models of multiple system atrophy.

Project description:Multiple system atrophy (MSA) is a predominantly sporadic, adult-onset, fatal neurodegenerative disease of unknown etiology. MSA is characterized by autonomic failure, levodopa-unresponsive parkinsonism, cerebellar ataxia and pyramidal signs in any combination. MSA belongs to a group of neurodegenerative disorders termed ?-synucleinopathies, which also include Parkinson's disease and dementia with Lewy bodies. Their common pathological feature is the occurrence of abnormal ?-synuclein positive inclusions in neurons or glial cells. In MSA, the main cell type presenting aggregates composed of ?-synuclein are oligodendroglial cells . This pathological hallmark, also called glial cytoplasmic inclusions (GCIs) , is associated with progressive and profound neuronal loss in various regions of the brain. The development of animal models of MSA is justified by the limited understanding of the mechanisms of neurodegeneration and GCIs formation, which is paralleled by a lack of therapeutic strategies. Two main types of rodent models have been generated to replicate different features of MSA neuropathology. On one hand, neurotoxin-based models have been produced to reproduce neuronal loss in substantia nigra pars compacta and striatum. On the other hand, transgenic mouse models with overexpression of ?-synuclein in oligodendroglia have been used to reproduce GCIs-related pathology. This chapter gives an overview of the atypical Parkinson's syndrome MSA and summarizes the currently available MSA animal models and their relevance for pre-clinical testing of disease-modifying therapies.

| S-EPMC4730554 | biostudies-literature

Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the frontal cortex of an individual with progressive supranuclear palsy

Project description: Not available

| EMPIAR-10765 | biostudies-other

Single particle cryo-EM dataset of sarkosyl-insoluble fraction from the nucleus accumbens of an individual with argyrophilic grain disease

Project description: Not available

| EMPIAR-10768 | biostudies-other