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PROVIDER: PRJEB52037 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Candidate biomarkers of EV-microRNA in detecting REM sleep behavior disorder and Parkinson’s disease
| PRJNA699177 | ENA
Project description:Gut microbiota across early stages of alpha-synucleinopathy
| PRJEB52086 | ENA
Project description:Examination of early phases of synucleinopathy when inclusions are present, but long before neurodegeneration occurs, is critical to both understanding disease progression and the development of disease modifying therapies. The rat alpha-synuclein (α-syn) preformed fibril (PFF) model induces synchronized synucleinopathy that recapitulates the pathological features of Parkinson’s disease (PD) and can be used to study synucleinopathy progression. In this model, phosphorylated α-syn (pSyn) inclusion-containing neurons and reactive microglia (major histocompatibility complex-II immunoreactive) peak in the substantia nigra pars compacta (SNpc) months before appreciable neurodegeneration. However, it remains unclear which specific genes are driving these phenotypic changes. To identify transcriptional changes associated with early synucleinopathy, we used laser capture microdissection of the SNpc paired with RNA sequencing (RNASeq). Precision collection of the SNpc allowed for the assessment of differential transcript expression in the nigral dopamine neurons and proximal glia. Transcripts upregulated in early synucleinopathy were mainly associated with an immune response, whereas transcripts downregulated were associated with neurotransmission and the dopamine pathway. A subset of 29 transcripts associated with neurotransmission/vesicular release and the dopamine pathway were verified in a separate cohort of males and females to confirm reproducibility. Within this subset, fluorescent in situ hybridization (FISH) was used to localize decreases in the Syt1 and Slc6a3 transcripts to pSyn inclusion-containing neurons. Identification of transcriptional changes in early synucleinopathy provides insight into the molecular mechanisms driving neurodegeneration.
2023-10-24 | GSE246112 | GEO
Project description:Microbiota for rapid eye movement sleep behavior disorder
| PRJDB9049 | ENA
Project description:The perioculomotor (pIII) region of the midbrain was postulated as a sleep-regulating center in the 1890s but largely neglected in subsequent studies. Using activity-dependent labeling and gene-expression profiling, we identified pIII neurons that promote non-REM (NREM) sleep.
2019-05-01 | GSE124681 | GEO
Project description:The synaptic protein α-synuclein is linked through genetics and neuropathology to the pathogenesis of Parkinson’s disease and related disorders. However, the mechanisms by which α-synuclein influences disease onset and progression are incompletely understood. To identify novel pathways and potential therapeutic targets we performed proteomic analysis in a highly penetrant new Drosophila model of α-synucleinopathy. We identified 476 significantly upregulated and 563 significantly downregulated proteins in heads from α-synucleinopathy model flies compared to controls. We then used multiple complementary analyses to identify and prioritize genes and pathways within the large set of differentially expressed proteins for functional studies. We performed Gene Ontology enrichment analysis, integrated our proteomic changes with human Parkinson’s disease genetic studies, and compared the α-synucleinopathy proteome with that of tauopathy model flies, which are relevant to Alzheimer’s disease and related disorders. These approaches identified GTP cyclohydrolase (GCH1) and folate metabolism as candidate mediators of α-synuclein neurotoxicity. In functional validation studies we found that knockdown of Drosophila Gch1 enhanced locomotor deficits in α-synuclein transgenic flies, while folate supplementation protected from α-synuclein toxicity. Our integrative analysis suggested that mitochondrial dysfunction was a common downstream mediator of neurodegeneration. Accordingly, Gch1 knockdown enhanced metabolic dysfunction in α-synuclein transgenic fly brains while folate supplementation partially normalized whole brain bioenergetics. Here we outline and implement an integrative approach to identify and validate potential therapeutic pathways using comparative proteomics and genetics and capitalizing on the facile genetic and pharmacological tools available in Drosophila.
2021-09-09 | PXD021312 | Pride
Project description:Parkinson’s disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking, and there are no robust biomarkers that can facilitate the development of such treatments or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson’s disease. We biochemically profiled the brain tissue and serum in a mouse model with progressive synucleinopathy propagation in the brain triggered by unilateral injection of preformed α-synuclein fibrils in the olfactory bulb. In total, we accurately identified and quantified 71 metabolites in the brain and 182 in serum using 1H NMR and targeted mass spectrometry, respectively. Using multivariate analysis, we accurately identified which metabolites explain the most variation between cases and controls. Using pathway enrichment analysis, we highlight significantly perturbed biochemical pathways in the brain and correlate these with the progression of the disease. Furthermore, we identified the top six discriminatory metabolites and were able to develop a model capable of identifying animals with the pathology from healthy controls with high accuracy (AUC (95% CI) = 0.861 (0.755–0.968)). Our study highlights the utility of metabolomics in identifying elements of Parkinson’s disease pathogenesis and for the development of early diagnostic biomarkers of the disease. </br></br> MS assays are reported in the current study MTBLS674 </br> NMR assay is reported in MTBLS640. </br><br/> Linked Studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS640' target='_blank'><span class='label label-success'>MTBLS640</span></a>
2019-02-07 | MTBLS674 | MetaboLights
Project description:Parkinson’s disease is the second most common neurodegenerative disease. In the vast majority of cases the origin is not genetic and the cause is not well understood, although progressive accumulation of α-synuclein aggregates appears central to the pathogenesis. Currently, treatments that slow disease progression are lacking, and there are no robust biomarkers that can facilitate the development of such treatments or act as aids in early diagnosis. Therefore, we have defined metabolomic changes in the brain and serum in an animal model of prodromal Parkinson’s disease. We biochemically profiled the brain tissue and serum in a mouse model with progressive synucleinopathy propagation in the brain triggered by unilateral injection of preformed α-synuclein fibrils in the olfactory bulb. In total, we accurately identified and quantified 71 metabolites in the brain and 182 in serum using 1H NMR and targeted mass spectrometry, respectively. Using multivariate analysis, we accurately identified which metabolites explain the most variation between cases and controls. Using pathway enrichment analysis, we highlight significantly perturbed biochemical pathways in the brain and correlate these with the progression of the disease. Furthermore, we identified the top six discriminatory metabolites and were able to develop a model capable of identifying animals with the pathology from healthy controls with high accuracy (AUC (95% CI) = 0.861 (0.755–0.968)). Our study highlights the utility of metabolomics in identifying elements of Parkinson’s disease pathogenesis and for the development of early diagnostic biomarkers of the disease. </br></br> NMR assay is reported in the current study MTBLS640. </br> MS assays are reported in MTBLS674. </br><br/> Linked Studies: <a href='https://www.ebi.ac.uk/metabolights/MTBLS674' target='_blank'><span class='label label-success'>MTBLS674</span></a>
2019-02-07 | MTBLS640 | MetaboLights
Project description:Sleep supports lifelong brain health and cognition. Sleep loss in early life can drive lasting changes in adult behavior, indicating sleep plays a distinct but poorly understood role supporting brain development. We systematically examined the molecular and behavioral adaptations and synaptic consequences of acute sleep deprivation (SD) in developing and adult mice. Developing mice lack robust adaptations to SD, exacerbating cognitive deficits. Synapse proteome and phosphoproteome analysis revealed profound vulnerability to SD in developing mice, including immediate impacts on synaptogenesis and key aspects of brain development. With maturation, a unified biochemical effect of sleep on synapses emerges, together with robust adaptations and resilience to SD. Our findings show sleep plays a distinct role in early life supporting synapse development, transitioning to homeostatic functions with maturation.
2024-10-08 | PXD047381 | Pride
Project description:Parkinson’s disease (PD) is increasing in prevalence, yet we lack readily available and non-invasive diagnostic biomarkers. An unbiased discovery proteomics study in plasma from PD patients and healthy controls (HC, phase 0) showed increased inflammation and decreased Wnt-signalling. To validate these findings, a targeted and multiplexed assay was developed and applied to a phase I cohort consisting of 99 de novo PD, 36 HC, and 18 subjects with polysomnography-confirmed isolated REM-sleep behaviour disorder (iRBD). In phase II, the multiplexed panel was refined and applied to a second cohort, focusing on the earliest stage of the disease by analysing 54 individuals with confirmed iRBD including longitudinal follow-up samples. A machine learning model, based on the expression of eight proteins, correctly identified all PD patients (phase I) and classified 79% of the iRBD as PD (phase II) up to 7 years before phenoconversion. Several of the identified biomarkers correlated with motor and non-motor symptom severity. This specific blood pattern was already evident in most iRBD cases, indicating pre-motor molecular events. This allows for the early identification of subjects at risk for PD in a blood test years before motor disease, which could support stratifying participants in future clinical trials aimed at preventing PD.
2024-03-12 | PXD041419 | panorama