Caenorhabditis elegans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA622398 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11482468_1.fastq.gz | Fastqsanger.gz | |||
| SRR11482468_2.fastq.gz | Fastqsanger.gz | |||
| SRR11482469_1.fastq.gz | Fastqsanger.gz | |||
| SRR11482469_2.fastq.gz | Fastqsanger.gz | |||
| SRR11482470_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Lewy body disorders are characterized by alpha-synucleinopathic inclusions that tend to develop in neurons extending long, thin, and unmyelinated fibers. It is unknown if this selective vulnerability reflects poor myelination per se. We have observed that preformed fibrils (PFFs) of alpha-synuclein tend to induce pathology in gray matter, even when infused into regions penetrated by white matter bundles. In addition, we found that levels of insoluble, hyperphosphorylated alpha-synuclein correlate inversely with myelin markers in the postmortem amygdala of men—but not women—with Lewy body disease. Thus, we tested if myelin disruption with pharmacologic or genetic tools exacerbates alpha-synucleinopathic lesions in a model of early-stage, limbic Lewy body disease. In genetically outbred CD-1 mice infused with PFFs in the caudal olfactory bulb, the myelin-disruptor cuprizone caused subtle exacerbation of α-synucleinopathy, but without impacting PFF-induced neuron loss or behavior deficits. Furthermore, in C57BL/6J mice heterozygous for myelin basic protein (Mbp+/shi), PFF-induced increases in the insolubility and hyperphosphorylation of alpha-synuclein were not amplified and histological outcomes were not markedly exacerbated. Given our observations of inverse correlations between α-synucleinopathy and myelin markers in the human male amygdala, Lewy body disease may disrupt myelination, rather than poor myelination status regulating the emergence of limbic α-synucleinopathy. This new perspective is reinforced by suppressed expression of select oligodendrocytic markers in the amygdalae of men with Lewy body disease compared to women. Thus, resilient neurons may defy the initial development of Lewy-related pathologies due to properties unrelated to myelination per se.
2025-05-20 | GSE297212 | GEO
Project description:Alzheimer’s disease and related dementias (ADRD), including Alzheimer’s disease (AD), frontotemporal dementia (FTD), Lewy body dementia (LBD), and mixed dementia are characterized by diverse pathologies and etiologies. ADRDs are typically distinguished based on combinations of associated pathologies in the brain such as amyloid, tau, TDP-43 inclusions, alpha-synuclein aggregates, and cerebral amyloid angiopathy, and these pathologies often co-occur even in cases clinically diagnosed as one disease. The heterogeneity of ADRDs presents significant challenges in model development for disease mechanism elucidation, drug discovery, and preclinical testing. Current animal models of ADRD fail to incorporate mixed pathologies and demonstrate low concordance with the diverse genetic, molecular, pathological, and cognitive features of human disease. Further, genetic background is critical for accurately modeling the complex genetic, molecular and cognitive features of late-onset AD in mice, and that incorporation of genetic diversity significantly improves concordance between mouse models and human patients in these parameters. Using CRISPR genome editing, we knocked-in several known human disease-causing mutations into C57BL/6J mice. Through serial breeding, we combined these KI mutations into various 3X, 4X, 5X and 6X knock-in models. We then crossed these 3X-5X models to various genetic backgrounds (C57BL/6J, DBA/2J, FVB/NJ, WSB/EiJ) to achieve a diverse F1 panel of genetically altered mice. Our goal was to maintain physiological expression levels of genes that induce commonly co-occurring pathologies in brain and peripheral tissues, while addressing these critical concerns often overlooked in most mouse models of neurodegenerative diseases (i.e., genetic diversity, late symptom onset, systemic expression of mutations, etc).
2025-04-05 | GSE293440 | GEO
Project description:Mutations in glucocerebrosidase (GBA) are the most prevalent genetic risk factor for Lewy body disorders (LBD) – collectively Parkinson’s disease, Parkinson’s disease dementia and dementia with Lewy bodies. Despite this genetic association, it remains unclear how GBA mutation contributes to the susceptibility of developing LBD. We investigated relationships between LBD-specific glucocerebrosidase deficits, GBA-related pathways, and α-synuclein levels in post-mortem brain tissue from LBD and controls with and without GBA mutations. Our study shows that LBD brains, regardless of GBA mutations, are characterised by altered sphingolipid metabolism, with prominent changes in ceramide species. Since extracellular vesicles (EV) could be involved in LBD pathogenesis by spreading disease linked lipids and proteins, we investigated EV derived from post-mortem cerebrospinal fluid (CSF) and brain tissue from GBA mutation carriers and non-carriers. EV purified from LBD post-mortem CSF and frontal cortex are heavily loaded with ceramides and neurodegeneration-linked proteins including alpha-synuclein and amyloid precursor protein. Our in vitro studies demonstrate that LBD EV constitute a “pathological package” capable of inducing aggregation of wild type alpha-synuclein, potentially through a combination of alpha-synuclein-ceramide interaction and the presence of pathological forms of alpha-synuclein. Together our findings indicate that abnormalities in ceramide metabolism are a feature of LBD, constituting a promising source of biomarkers. GBA mutation likely accelerates the pathological process occurring in sporadic LBD, probably through endolysosomal deficiency, but does not induce alpha-synucleinopathy since healthy normal GBA mutation carriers without alpha-synuclein pathology occur.
2021-11-02 | PXD026980 | Pride
Project description:Lewy body dementia promotion by air pollutants
| PRJNA1263837 | ENA
Project description:Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that is characterized by the selective loss of midbrain dopamine (DA)-producing neurons and the formation of α-synuclein (α-syn)-containing inclusions named Lewy bodies (LBs). Here, we report that the loss of glucocerebrosidase (GCase), coupled with α-syn overexpression, result in substantial accumulation of detergent-resistant α-syn aggregates and Lewy body-like inclusions (LBLIs) in human midbrain-like organoids (hMLOs). These LBLIs exhibit a highly similar structure to PD-associated LBs, by displaying a spherically symmetric morphology with an eosinophilic core, and containing α-syn and ubiquitin. Importantly, hMLOs generated from PD patient-derived inducible pluripotent stem cells (iPSCs) harboring SNCA triplication also exhibit subsequent degeneration of DA neurons and LBLI formation upon chronic GCase inhibitor treatment. Taken together, our hMLOs harbouring two major PD risk factors (GCase deficiency and overproduced α-syn) successfully recapitulate major pathophysiological signatures of the disease, and highlight the broad utility of brain organoid technology in modeling human neurodegenerative diseases.
2021-08-13 | E-MTAB-7302 | biostudies-arrayexpress
Project description:Recent studies indicate that the adaptive immune system plays a role in Lewy body dementia (LBD). However, the mechanism regulating T cell brain homing in LBD is unknown. Here, we observed T cells adjacent to Lewy bodies and dopaminergic neurons in post-mortem LBD brains. Single-cell RNA sequencing of cerebrospinal fluid (CSF) identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Furthermore, we observed clonal expansion and upregulated Interleukin 17A expression by CD4+ T cells stimulated with a phosphorylated α-synuclein epitope. Thus, CXCR4-CXCL12 signaling may represent a mechanistic target for inhibiting pathological interleukin-17-producing T cell trafficking in LBD.
2021-09-14 | GSE141578 | GEO
Project description:Recent studies indicate a role of the adaptive immune system in Lewy body dementia (LBD). However, the mechanisms regulating T cell brain homing in LBD remain unknown. Here, we demonstrate interaction of T cells with Lewy bodies and with dopaminergic neurons in post-mortem LBD brains. Single cell RNA sequencing of cerebrospinal fluid (CSF) cells identified upregulated expression of C-X-C Motif Chemokine Receptor 4 (CXCR4) in CD4+ T cells in LBD. CSF protein levels of the CXCR4 ligand, C-X-C Motif Chemokine Ligand 12 (CXCL12) were associated with neuroaxonal damage in LBD. Finally, we demonstrate clonal expansion and upregulated Interleukin 17A by CD4+ T cells stimulated with phosphorylated α-synuclein. Cumulatively, these results indicate CXCR4-CXCL12 signaling as a mechanistic target for inhibiting pathological T cell trafficking in LBD.
2021-09-14 | GSE161192 | GEO
Project description:Evidence links air pollution to dementia, yet its role in Lewy body dementia (LBD) remains unclear. Here we show in a cohort of 56.5 million individuals across the U.S. that PM2.5 exposure significantly raises LBD risk. Mechanistically, we find PM2.5 exposure leads to brain atrophy in wild-type mice, an effect not seen in α-synuclein (αSyn)-deficient mice. PM2.5 exposure generates a highly pathogenic αSyn strain, PM-PFF, with enhanced proteinase K-resistance and neurotoxicity, resembling αSyn LBD strains. PM2.5 samples from China, the U.S., and Europe consistently induce proteinase-resistant αSyn strains and in vivo pathology. Transcriptomic analyses reveal shared responses between PM2.5-exposed mice and LBD patients, underscoring PM2.5’s role in LBD and the stresses the need for interventions to reduce air pollution and its associated neurological disease burden.
2025-11-13 | GSE297423 | GEO