Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA832075 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Gastrointestinal (GI) dysfunction precedes motor symptoms in Parkinson disease (PD), implicating the enteric nervous system (ENS) in early disease pathogenesis. However, how the PD-associated protein alpha synuclein (alpha syn) contributes to ENS dysfunction, and whether this is influenced by inflammation, remains unresolved. Here, we show that tumor necrosis factor alpha (TNF alpha) increases alpha syn accumulation at mitochondria, disrupts the malate-aspartate shuttle (MAS), and induces a metabolic shift toward glutamine oxidation in iPSC derived enteric neural lineages (ENLs) from PD patients carrying alpha syn gene triplications. This metabolic rewiring leads to mitochondrial dysfunction, NAD+ depletion, and oxidative stress. Targeting glutamate metabolism with Chicago Sky Blue 6B restores mitochondrial function and reverses TNF alpha induced metabolic impairment. Combined transcriptomic and histological analyses of human gut tissue show that inflammation-associated MAS suppression and alpha syn upregulation are not confined to PD but are general hallmarks of intestinal inflammation. These findings highlight a conserved metabolic vulnerability in the ENS and establish iPSC ENLs as a powerful platform for modeling early inflammatory disease mechanisms.
2025-06-27 | MSV000098366 | MassIVE
Project description:Gastrointestinal (GI) dysfunction precedes motor symptoms in Parkinson disease (PD), implicating the enteric nervous system (ENS) in early disease pathogenesis. However, how the PD-associated protein alpha synuclein (alpha syn) contributes to ENS dysfunction, and whether this is influenced by inflammation, remains unresolved. Here, we show that tumor necrosis factor alpha (TNF alpha) increases alpha syn accumulation at mitochondria, disrupts the malate-aspartate shuttle (MAS), and induces a metabolic shift toward glutamine oxidation in iPSC derived enteric neural lineages (ENLs) from PD patients carrying alpha syn gene triplications. This metabolic rewiring leads to mitochondrial dysfunction, NAD+ depletion, and oxidative stress. Targeting glutamate metabolism with Chicago Sky Blue 6B restores mitochondrial function and reverses TNF alpha induced metabolic impairment. Combined transcriptomic and histological analyses of human gut tissue show that inflammation-associated MAS suppression and alpha syn upregulation are not confined to PD but are general hallmarks of intestinal inflammation. These findings highlight a conserved metabolic vulnerability in the ENS and establish iPSC ENLs as a powerful platform for modeling early inflammatory disease mechanisms.
2025-06-28 | MSV000098371 | MassIVE
Project description:Neuroinflammation and accumulation of alphα-synuclein (α-syn) are core features of Parkinson disease (PD). We found that α-syn-induced neuroinflammation is driven by antigen presentation from CNS resident macrophages. A subset of these, border-associated macrophages (BAMs), expand and express genes and proteins necessary for immune cell recruitment, infiltration, and antigen presentation, whereas depletion of BAMs prevents neuroinflammation and neurodegeneration. These results point to a critical role for BAMs in initiating PD pathogenesis.
2021-06-20 | GSE178498 | GEO
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls
2015-09-07 | PXD002259 | Pride
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls.
2015-09-07 | PXD002260 | Pride
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls.
2015-09-07 | PXD002258 | Pride
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls
2015-09-07 | PXD002262 | Pride
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls.
2015-09-07 | PXD002257 | Pride
Project description:Fibrillar α-Synuclein (α-Syn) is the principal component of Lewy bodies which are evident in individuals affected by Parkinson disease (PD). This neuropathologic form of α-Syn contributes to PD progression and propagation of exogeneous α-Syn between neurons has been demonstrated. In order to identify proteins interacting with extracellularly applied α-syn assemblies (either oligomeric or fibrillar α -syn) and identify in particular plasma membrane proteins exposed extracellularly, we exposed pure-neuronal cultures to oligomeric and fibrillar α-syn for 10 min, pulled down the complex, and identified the associated proteins using a proteomic-based approach. Using pull-down of whole cell lysates and MS, we have identified proteins interacting with extracellularly applied α-syn in three different conditions. Each condition consisted in three experimental replicates of cells exposed 10 min to α-syn assemblies and the non-treated cells used as controls
2015-09-07 | PXD002256 | Pride