AVE0991 regulates HOTAIRM1/miR-223-3p/α-synuclein to improve behaviour and protect dopaminergic neurons in human α-syn (A53T) overexpressing mice
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ABSTRACT:
PROVIDER: PRJNA1021164 | ENA |
REPOSITORIES: ENA
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Project description:Objective: Parkinson's disease (PD) is part of a common type of neurodegenerative disease. AVE0991, a non-peptide analogue of Ang-(1-7), by which the progression of PD has been discovered to be ameliorated, but the specific mechanism whereby AVE0991 modulates the progression of PD remains unclear. Materials and Methods: During the study, the mice overexpressing of human α-syn(A53T) were established to simulate PD pathology, and we also constructed an in vitro model of mouse dopaminergic neurons overexpressing hα-syn(A53T). The [18F] FDG-PET/CT method was also employed to assess FDG uptake in human α-syn(A53T) overexpressing mice. Level of Lnc HOTAIRM1, miR-223-3p were detected via RT-qPCR. Flow cytometry was deployed to assay cell apoptosis. Results: AVE0991 improved behavior disorder and decreased α-syn expression in the substantia nigra in mice with Parkinson's disease. AVE0991 inhibited apoptosis of dopaminergic neurons overexpressing hα-syn(A53T) by LncRNA HOTAIRM1. MiR-223-3p binds to HOTAIRM1 as a ceRNA and directly targets α-syn. Conclusion: The angiotensin-(1–7) analogue AVE0991 targeted the HOTAIRM1/miR-223-3p axis to degrade α-synuclein in PD mice, and showed neuroprotection in vitro.
2024-11-06 | GSE244050 | GEO
Project description:LC-MS/MS analyses were performed on soluble alpha-Syn purified from PD and various alpha-Synucleinopathies to systematically explore the landscape of post-translational modifications (PTMs) on soluble alpha-Syn, leading to the identification of a large number of novel alpha-Syn PTMs.
2022-10-30 | MSV000090618 | MassIVE
Project description:Kuznetsov2016(II) - α-syn aggregation
kinetics in Parkinson's
This theoretical model uses 2-step Finke-Watzky (FW) kinetics
todescribe the production, misfolding, aggregation, transport and
degradation of α-syn that may lead to Parkinson's Disease
(PD). Deregulated α-syn degradation is predicted to be
crucialfor PD pathogenesis.
This model is described in the article:
What can trigger the onset
of Parkinson's disease - A modeling study based on a
compartmental model of α-synuclein transport and aggregation in
neurons.
Kuznetsov IA, Kuznetsov AV.
Math Biosci 2016 Aug; 278: 22-29
Abstract:
The aim of this paper is to develop a minimal model
describing events leading to the onset of Parkinson's disease
(PD). The model accounts for α-synuclein (α-syn) production in
the soma, transport toward the synapse, misfolding, and
aggregation. The production and aggregation of polymeric α-syn
is simulated using a minimalistic 2-step Finke-Watzky model. We
utilized the developed model to analyze what changes in a
healthy neuron are likely to lead to the onset of α-syn
aggregation. We checked the effects of interruption of α-syn
transport toward the synapse, entry of misfolded (infectious)
α-syn into the somatic and synaptic compartments, increasing
the rate of α-syn synthesis in the soma, and failure of α-syn
degradation machinery. Our model suggests that failure of α-syn
degradation machinery is probably the most likely cause for the
onset of α-syn aggregation leading to PD.
This model is hosted on
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and identified by:
BIOMD0000000615.
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2024-09-02 | BIOMD0000000615 | BioModels
Project description:To investigate the target genes of HOTAIRM1 in glioma cells, we conducted a lncRNA + mRNA expression microarray analysis to identify novel HOTAIRM1 regulating genes. Three glioma cell lines U87MG, T98G and A172 stably knockdown HOTAIRM1 were used as the experiments models. We conservatively established a minimum of 2-fold difference between shHOTAIRM1 (knockdown HOTAIRM1) and shNT (control group), and identified 10 up-regulated and 22 down-regulated genes that met the threshold in all cell lines.
2021-12-26 | GSE192627 | 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 | 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 | PXD002256 | 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 | 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 | 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 | PXD002257 | Pride