Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: GSE51923
PROVIDER: PRJNA225814 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Microarray expression analysis in idiopathic and LRRK2-associated Parkinson's disease
| PRJNA131367 | ENA
Project description:DNA methylation analysis in idiopathic and LRRK2-associated Parkinson's disease (PD)
| PRJNA225815 | ENA
Project description:Brain transcriptomic profiling in idiopathic and LRRK2-associated Parkinson's disease
| PRJNA151407 | ENA
Project description:Idiopathic and LRRK2-associated Parkinson's disease
| PRJNA225813 | ENA
Project description:Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study, we generated H9 hESC harboring LRRK2 (G2019S) mutation by gene knockin. Wildtype and LRRK2 mutant hESC were differentiated into NSC using a chemically defined protocol. LRRK2 mutant NSC were treated with or without the LRRK2 kinase specific inhibitor (LRRK2-IN-1). Global gene expression analysis was performed to assess the overall similarity of gene expression profiles among three NSC groups (wildtype; LRRK2 mutant; LRRK2 mutant with inhibitor treatment).
2012-10-17 | E-GEOD-36321 | biostudies-arrayexpress
Project description:<p>Rationale: Sex and type of Parkinson's disease (PD) significantly influence onset age, clinical manifestations, treatment response, disease progression and life expectancy. However, the selective influence of idiopathic and familial forms of PD in disrupting blood metabolome profiles across genders remains unclear.</p><p>Methods: We conducted an untargeted 1H NMR-based metabolomics study in a large cohort of clinically and genetically well-characterized patients and controls (n=385), which included: i) 56 women and 65 men diagnosed with idiopathic PD; ii) 60 women and 64 men with a familial form of PD; iii) 80 men and 60 women serving as healthy control groups.</p><p>Results: Multivariate Analysis (MVA) did not reveal differences in serum metabolomes between idiopathic and familial PD patients in both sexes. Similarly, MVA did not show significant variation among blood metabolomes of patients carrying distinct pathogenic variants, including LRRK2, TMEM175, PRKN, PINK1, PARK7 and GBA1. MVA indicates remarkable metabolome differences between idiopathic and familial subtypes compared to healthy controls. Notably, 1H NMR-based metabolomics unveiled a striking gender effect in influencing metabolome dysregulation across idiopathic or familial patients compared to matched controls. Specifically, our results indicate that amino acids, glutathione biosynthesis, energy homeostasis pathways, phospholipids and ketone body metabolism alterations are critically associated with the sex and genotype of PD individuals. However, regardless of the specific disease type, MVA consolidates the evidence that more pronounced blood metabolome dysregulations occurred in males than women with the same form of PD.</p><p>Conclusion: We reveal that men and women exhibit distinct serum metabolome dysregulations across idiopathic and familial forms of PD compared to healthy controls, further indicating the key role of gender and genetic background in controlling varying pathophysiological features of the disease.</p>
2025-09-03 | MTBLS11187 | MetaboLights
Project description:Gain-of kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause Parkinson’s disease (PD), albeit with incomplete and age-dependent penetrance, offering the prospect of disease-modifying treatment strategies via LRRK2 kinase inhibition. LRRK2 phosphorylates a subgroup of RabGTPases including Rab10 and pathogenic mutations enhance LRRK2-mediated phosphorylation of Rab10 at Thr73. In this study we analyse LRRK2 dependent Rab10Thr73 phosphorylation in human peripheral blood neutrophils isolated from 101 individuals using quantitative immunoblotting and mass spectrometry. Our cohort includes 42 LRRK2 mutation carriers (21 with the G2019S mutation that resides in the kinase domain and 21 with the R1441G mutation that lies within the ROC-COR domain), 27 patients with idiopathic PD, and 32 controls. We show that LRRK2 dependent Rab10 Thr73 phosphorylation is significantly elevated in all R1441G LRRKR2 mutation carriers irrespective of disease status. PD manifesting and non-manifesting G2019S mutation carriers as well as idiopathic PD samples did not display elevated Rab10 Thr73 phosphorylation. Furthermore, we analysed brain samples of 10 G2019S and 1 R1441H mutation carriers as well as 10 individuals with idiopathic PD and 10 controls. We find high variability for pRab10Thr73 phosphorylation amongst donors irrespective of genetic and disease state. We conclude that in vivo LRRK2 dependent pRab10Thr73 analysis in human peripheral blood neutrophils is a specific and robust biomarker for LRRK2 kinase activation for individuals with mutations such as R1441G that enhance pRab10Thr73 phosphorylation over 2-fold. We provide the first evidence that the LRRK2 R1441G mutation enhances LRRK2 kinase activity in a primary human cell.
2021-09-10 | PXD024898 | Pride
Project description:LRRK2 mutations are the most common genetic cause of Parkinson’s disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
2011-11-10 | GSE23290 | GEO
Project description:Genetic mutations on leucine-rich repeat kinase 2 (LRRK2) have been associated with an increased risk of Parkinson's disease. The Gly2019Ser (G2019S) mutation on LRRK2 gene is a relatively common cause of familial Parkinson's disease in Caucasian population. In this study, we generated H9 hESC harboring LRRK2 (G2019S) mutation by gene knockin. Wildtype and LRRK2 mutant hESC were differentiated into NSC using a chemically defined protocol.
2012-10-17 | GSE36321 | GEO
Project description:LRRK2 mutations are the most common genetic cause of Parkinson’s disease (PD). We performed a whole-genome RNA profiling of locus coeruleus post-mortem tissue from idiopathic PD (IPD) and LRRK2-associated PD patients. The differentially expressed genes found in IPD and LRRK2-associated PD were involved in the gene ontology terms of synaptic transmission and neuron projection. In addition, in the IPD group we found associated genes belonging to the immune system. Pathway analysis of the differentially expressed genes in IPD was related with neuroactive-ligand receptor interaction and with immune system pathways. Specifically, the analysis highlighted differential expression of genes located in the chromosome 6p21.3 belonging to the class II HLA. Our findings support the hypothesis of a potential role of neuroinflammation and the involvement of the HLA genetic area in IPD pathogenesis. Future studies are necessary to shed light on the relation of immune system related pathways in the etiopathogenesis of PD.
2012-06-01 | GSE34516 | GEO