Saccharomyces cerevisiae
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA106153 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Parkinson's disease genes VPS35 and EIF4G1 interact genetically and converge on alpha-synuclein
| PRJNA270712 | ENA
Project description:Parkinson's disease (PD) is a common human neurodegenerative movement disorder. Studies of the genetic forms of PD have helped to reveal disease mechanisms. Functional interactions between some Parkinson's disease (PD) genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1 and alpha-synuclein, a protein with a key role in the pathogenesis of both sporadic and familial PD. We extend our findings from yeast to an animal model and show these interactions are conserved in neurons. We also connect VPS35 impairments to neurodegeneration in alpha-synuclein transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to alpha-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future genetic and functional interrogation. Ribosome profiling (RiboSeq) of wild type and VPS35 deletion yeast strains, with or without overexpression of the TIF4631 initiation factor
2014-12-19 | E-GEOD-64304 | biostudies-arrayexpress
Project description:Cellular toxicities of alpha-synuclein manifest through multiple pathways, including mitochondrial dysfunction and the inhibition of vesicle trafficking. Several defects can be ameliorated by small molecule suppressors that antagonize toxicity in model systems ranging from yeast to neurons. Connections between these distinct pathologies may be central to Parkinson Disease and to therapeutic strategies. First, yeast cultures with 1 or 2 copies of human alpha-synuclein were profiled during a time series of 0 to 6 hours. Second, to investigate any potential rescue of alpha-synuclein toxicity, one of a series of six compounds: compound 1 ((4-(3-iodophenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); compound 2 (4-(3-bromophenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); compound 3 (4-(5-bromo-2-fluorophenyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 4 (4-(3-bromo-4-fluorophenyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 5 (4-(4-ethyl)-6,7-dimethyl-3,4-dihydro-2(1H)-quinolinone); compound 6 ((4R)-6-bromo-4-(4-ethylphenyl)-3,4-dihydrobenzo[h]quinolin-2(1H)-one); was introduced and the expression profile assayed at 4 hours.
2010-01-04 | GSE11633 | GEO
Project description:In order to investigate the effect of Alpha-Ketoglutarate (AKG) on p-α-synuclein in substantia nigra of Parkinson's disease (PD) model mice (C57BL/6), we profiled substantia nigra from wild-type (WT), AAV-α-synuclein (α-Syn), AKG and α-Syn-AKG in male mice by RNA sequencing (RNA-seq).
2022-10-02 | GSE214446 | GEO
Project description:Parkinson's disease (PD) is a common human neurodegenerative movement disorder. Studies of the genetic forms of PD have helped to reveal disease mechanisms. Functional interactions between some Parkinson's disease (PD) genes, like PINK1 and parkin, have been identified, but whether other ones interact remains elusive. Here we report an unexpected genetic interaction between two PD genes, VPS35 and EIF4G1. We provide evidence that EIF4G1 upregulation causes defects associated with protein misfolding. Expression of a sortilin protein rescues these defects, downstream of VPS35, suggesting a potential role for sortilins in PD. We also show interactions between VPS35, EIF4G1 and alpha-synuclein, a protein with a key role in the pathogenesis of both sporadic and familial PD. We extend our findings from yeast to an animal model and show these interactions are conserved in neurons. We also connect VPS35 impairments to neurodegeneration in alpha-synuclein transgenic mice. Our studies reveal unexpected genetic and functional interactions between two seemingly unrelated PD genes and functionally connect them to alpha-synuclein pathobiology in yeast, worms, and mouse. Finally, we provide a resource of candidate PD genes for future genetic and functional interrogation.
2014-12-19 | GSE64304 | GEO
Project description:Randomized CRISPR-Cas Transcriptional Perturbation Screening Reveals Protective Genes against Alpha-Synuclein Toxicity
| PRJNA345160 | ENA
Project description:Altogether results show that peroxidase activity of cytochrome c contributes to α-synuclein radical formation and oligomerization, and that α-synuclein through its co-localization with cytochrome c or on it's own, affects several biological pathways which contribute to increased neuronal death in Maneb and paraquat (MP)-induced model of Parkinson's disease.
2016-11-29 | GSE89562 | GEO
Project description:Thorium (232Th), an actinoide element, is among the most common and naturally occurring radioactive materials distributed in our environment. Thorium has been used as a radiographic contrast agent (thorotrast) from 1930 to 1955, and many studies on its effects to the human body have been reported. Once thorium is injected in the body, the risk of cancer is increased by the direct bombardment from alpha-particle with high linear energy transfer during decay of Thorium. However, these many reports focus on the irradiation damage by long-term exposure of thorium. The acute toxicity of thorium is greater risk from the chemical toxicity than from the radiological toxicity. Here, we evaluated the effect of thorium from the stand point of chemical toxicity using yeast DNA microarray. In this experiment, genes that contribute to “C-compound and carbohydrate metabolism”, “energy”, and “cell rescue, defense and virulence” were significantly induced. These genes were classified into oxidative stress, glycogen and trehalose metabolism, sugar transport, and cell wall damage. On the contrary, only one gene related to DNA damage was detected. These results indicate that thorium causes the damage of cell wall and induces the oxidative stress. In order to overcome oxidative stress, yeast cells promote the glycogen and trehalose metabolisms and shift to anaerobic fermentation. Keywords: stress response
2007-11-01 | GSE9463 | GEO
Project description:The full complement of molecular pathways contributing to Parkinson’s disease (PD) pathogenesis remains unknown. Here, to address this issue, we began by using a high-resolution variant of functional magnetic resonance imaging (fMRI) to pinpoint brainstem regions differentially affected by, and resistant to, the disease. Then, relying on the imaging information as a guide, we profiled gene expression levels of postmortem brain samples and used a factorial statistical model to identify a disease related decrease in the expression of the polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a series of studies were performed to confirm the pathogenic relevance of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, while Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, we genotyped PD patients and controls and isolated a rare but novel variant in the SAT1 gene, although the functional significance of this genetic variant was not identified. Taken together, the results suggest that the polyamine pathway contributes to PD pathogenesis.
2010-08-19 | GSE19587 | GEO
Project description:Detailed analysis of disease-affected tissue provides insight into molecular mechanisms contributing to pathogenesis. Substantia nigra, striatum and cortex are functionally connected with increasing degrees of alpha-synuclein pathology in Parkinson's disease. Functional and causal pathway analysis of gene expression and proteomic alterations in these three regions revealed pathways that correlated with deposition of alpha-synuclein. Microarray and RNAseq experiments revealed previously unidentified causal changes related to oligodendrocyte function and synaptic vesicle release and other changes were reflected across all brain regions. Importantly a subset of these changes were replicated in Parkinson's disease blood. Proteomic assessment revealed alterations in mitochondria and vesicular transport proteins that preceded gene gene expression changes indicating defects in translation and/or protein turnover. Our combined approach of proteomics, RNAseq and microarray analyses provides a comprehensive view of the molecular changes that accompany alpha-synculein pathology in Parkinson's disease, and may be instrumental in understanding and diagnosing Parkinson's disease progression. Substantia Nigra (3 normal, 3 PD), Striatum (6 normal, 6 PD), Cortex (5 normal, 5 PD), Cortex non-PD neurodegeneration (2 normal, 3 DLB). Note Sample X201264 was used both for Cortex normal and for Cortex nonPD normal
2014-09-01 | E-GEOD-54282 | biostudies-arrayexpress