Parkinson's disease mouse brain proteome profiling
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Orbitrap Fusion
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: 
Sung Jung
PROVIDER: MSV000080437 | MassIVE | Sun Dec 25 20:45:00 GMT 2016
SECONDARY ACCESSION(S): PXD005626
REPOSITORIES: MassIVE
Publications
An Anatomically Resolved Mouse Brain Proteome Reveals Parkinson Disease-relevant Pathways.
Jung Sung Yun SY Choi Jong Min JM Rousseaux Maxime W C MW Malovannaya Anna A Kim Jean J JJ Kutzera Joachim J Wang Yi Y Huang Yin Y Zhu Weimin W Maity Suman S Zoghbi Huda Yahya HY Qin Jun J
Molecular & cellular proteomics : MCP 20170202 4
Here, we present a mouse brain protein atlas that covers 17 surgically distinct neuroanatomical regions of the adult mouse brain, each less than 1 mm<sup>3</sup> in size. The protein expression levels are determined for 6,500 to 7,500 gene protein products from each region and over 12,000 gene protein products for the entire brain, documenting the physiological repertoire of mouse brain proteins in an anatomically resolved and comprehensive manner. We explored the utility of our spatially define ...[more]
Similar Datasets
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of VTA were investigated comparing late middle-aged (18 months old) to young (2 months old) mice.
2013-05-29 | GSE45044 | GEO
Project description:Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms. This SuperSeries is composed of the following subset Series: GSE20168: Transcriptional analysis of prefrontal area 9 in Parkinson's disease GSE20291: Transcriptional analysis of putamen in Parkinson's disease GSE20292: Transcriptional analysis of whole substantia nigra in Parkinson's disease Refer to individual Series
2010-03-23 | E-GEOD-20295 | biostudies-arrayexpress
Project description:Substantia nigra pars compacta (SNpc) is highly sensitive to normal aging and selectively degenerates in Parkinson's disease. However, ventral tegmental area (VTA), a region adjacent to SNpc, is less affected in PD. Until now, molecular mechanisms behind VTA aging have not been fully investigated using high throughput techniques. Here, aging-associated early changes in transcriptome of VTA were investigated comparing late middle-aged (18 months old) to young (2 months old) mice. Three age groups of C57 wild type mice were used in microarray analysis: young (2 months old), middle aged (10 months old), and late-middle aged (18 months old) mice. Four replicates were included in each age group and each replicate was pooled from 5 mice (5 mice/replicate x 4 replicates x 3 age groups). Total RNA was isolated from VTA for hybridization on Affymetrix microarrays.
2013-05-29 | E-GEOD-45044 | biostudies-arrayexpress
Project description:Cis-regulatory elements (CREs) dictate spatiotemporal expression and tissue specificity of proximal genes. However, when in a transgenic state, many of them become highly vulnerable to RNA-Directed DNA Methylation (RdDM) that is often transcriptionally deleterious and biologically detrimental. This transgene-specific RdDM vulnerability suggests the existence of anti-RdDM elements (AREs) to defend CREs against de novo methylation in vivo. In this work, we identify such an ARE at the Arabidopsis AGAMOUS (AG) locus, which includes a physically separated enhancer and promoter, both of which are highly vulnerable to transgene silencing. We demonstrate that this ARE effectively represses RdDM activity at its cognate and heterologous CREs via the inhibition of transcription and processing of potent non-coding RNAs (ncRNAs), which act as substrates for the biogenesis of 24-nt small interfering RNAs (siRNAs) that guide RdDM. Furthermore, we establish that the ARE exploits hypermethylation in a 108-bp internal region (referred to as M1) as a regulatory signal to recruit methyl reader SU(VAR)3-9 homolog 1 (SUVH1), as well as Harbinger transposon-derived protein 2 (HDP2) associated with HDP1, to carry out ARE-imposed transcriptional and post-transcriptional repression, with the former mediating the repression of ncRNA transcription and the latter repressing both ncRNA transcription and processing. We also show that M1 methylation is indispensable for the repression of methylation in an adjacent, methylation-vulnerable 737-bp region (dubbed M2) to safeguard the ARE’s functional integrity. Taken together, the present study uncovers a novel anti-RdDM element that defends CREs against ncRNA-dependent, siRNA-driven, and methylation-imposed epigenetic interference to safeguard their regulatory integrity.
2023-09-21 | GSE228513 | GEO
Project description:Cis-regulatory elements (CREs) dictate spatiotemporal expression and tissue specificity of proximal genes. However, when in a transgenic state, many of them become highly vulnerable to RNA-Directed DNA Methylation (RdDM) that is often transcriptionally deleterious and biologically detrimental. This transgene-specific RdDM vulnerability suggests the existence of anti-RdDM elements (AREs) to defend CREs against de novo methylation in vivo. In this work, we identify such an ARE at the Arabidopsis AGAMOUS (AG) locus, which includes a physically separated enhancer and promoter, both of which are highly vulnerable to transgene silencing. We demonstrate that this ARE effectively represses RdDM activity at its cognate and heterologous CREs via the inhibition of transcription and processing of potent non-coding RNAs (ncRNAs), which act as substrates for the biogenesis of 24-nt small interfering RNAs (siRNAs) that guide RdDM. Furthermore, we establish that the ARE exploits hypermethylation in a 108-bp internal region (referred to as M1) as a regulatory signal to recruit methyl reader SU(VAR)3-9 homolog 1 (SUVH1), as well as Harbinger transposon-derived protein 2 (HDP2) associated with HDP1, to carry out ARE-imposed transcriptional and post-transcriptional repression, with the former mediating the repression of ncRNA transcription and the latter repressing both ncRNA transcription and processing. We also show that M1 methylation is indispensable for the repression of methylation in an adjacent, methylation-vulnerable 737-bp region (dubbed M2) to safeguard the ARE’s functional integrity. Taken together, the present study uncovers a novel anti-RdDM element that defends CREs against ncRNA-dependent, siRNA-driven, and methylation-imposed epigenetic interference to safeguard their regulatory integrity.
2023-09-21 | GSE228515 | GEO
Project description:Cis-regulatory elements (CREs) dictate spatiotemporal expression and tissue specificity of proximal genes. However, when in a transgenic state, many of them become highly vulnerable to RNA-Directed DNA Methylation (RdDM) that is often transcriptionally deleterious and biologically detrimental. This transgene-specific RdDM vulnerability suggests the existence of anti-RdDM elements (AREs) to defend CREs against de novo methylation in vivo. In this work, we identify such an ARE at the Arabidopsis AGAMOUS (AG) locus, which includes a physically separated enhancer and promoter, both of which are highly vulnerable to transgene silencing. We demonstrate that this ARE effectively represses RdDM activity at its cognate and heterologous CREs via the inhibition of transcription and processing of potent non-coding RNAs (ncRNAs), which act as substrates for the biogenesis of 24-nt small interfering RNAs (siRNAs) that guide RdDM. Furthermore, we establish that the ARE exploits hypermethylation in a 108-bp internal region (referred to as M1) as a regulatory signal to recruit methyl reader SU(VAR)3-9 homolog 1 (SUVH1), as well as Harbinger transposon-derived protein 2 (HDP2) associated with HDP1, to carry out ARE-imposed transcriptional and post-transcriptional repression, with the former mediating the repression of ncRNA transcription and the latter repressing both ncRNA transcription and processing. We also show that M1 methylation is indispensable for the repression of methylation in an adjacent, methylation-vulnerable 737-bp region (dubbed M2) to safeguard the ARE’s functional integrity. Taken together, the present study uncovers a novel anti-RdDM element that defends CREs against ncRNA-dependent, siRNA-driven, and methylation-imposed epigenetic interference to safeguard their regulatory integrity.
2023-09-21 | GSE228514 | GEO
Project description:Parkinson’s disease (PD) is characterized by multiple symptoms including olfactory dysfunction, whose underlying mechanisms remain unclear. Here, we explored pathologic changes in the olfactory pathway of transgenic (Tg) mice of both sexes expressing the human A30P mutant α-synuclein (α-syn; α-syn-Tg mice) at 6–7 and 12–14 months of age, representing early and late-stages of motor progression, respectively. α-Syn-Tg mice at late stages exhibited olfactory behavioral deficits, which correlated with severe α-syn pathology in projection neurons (PNs) of the olfactory pathway. In parallel, olfactory bulb (OB) neurogenesis in α-syn-Tg mice was reduced in the OB granule cells at six to seven months and OB periglomerular cells at 12–14 months, respectively, both of which could contribute to olfactory dysfunction. Proteomic analyses showed a disruption in endocytic and exocytic pathways in the OB during the early stages which appeared exacerbated at the synaptic terminals when the mice developed olfactory deficits at 12–14 months. Our data suggest that (1) the α-syn-Tg mice recapitulate the olfactory functional deficits seen in PD; (2) olfactory structures exhibit spatiotemporal disparities for vulnerability to α-syn pathology; (3) α-syn pathology is restricted to projection neurons in the olfactory pathway; (4) neurogenesis in adult α-syn-Tg mice is reduced in the OB; and (5) synaptic endocytosis and exocytosis defects in the OB may further explain olfactory deficits.
2023-01-13 | PXD039396 | Pride
Project description:This a model from the article:
The canine virtual ventricular wall: a platform for dissecting pharmacological
effects on propagation and arrhythmogenesis.
Benson AP, Aslanidi OV, Zhang H, Holden AV. Prog Biophys Mol Biol
2008 Jan-Apr;96(1-3):187-208 17915298
,
Abstract:
We have constructed computational models of canine ventricular cells and
tissues, ultimately combining detailed tissue architecture and heterogeneous
transmural electrophysiology. The heterogeneity is introduced by modifying the
Hund-Rudy canine cell model in order to reproduce experimentally reported
electrophysiological properties of endocardial, midmyocardial (M) and epicardial
cells. These models are validated against experimental data for individual ionic
current and action potential characteristics, and their rate dependencies. 1D
and 3D heterogeneous virtual tissues are constructed, with detailed tissue
architecture (anisotropy and orthotropy, due to fibre orientation and sheet
structure) of the left ventricular wall wedge extracted from a diffusion tensor
imaging data set. The models are used to study the effects of tissue
heterogeneity and class III drugs on transmural propagation and tissue
vulnerability to re-entry. We have determined relationships between the
transmural dispersion of action potential duration (APD) and the vulnerable
window in the 1D virtual ventricular wall, and demonstrated how changes in the
transmural heterogeneity, and hence tissue vulnerability, can lead to generation
of re-entry in the 3D ventricular wedge. Two class III drugs with opposite
qualitative effects on transmural APD heterogeneity are considered: d-sotalol
that increases transmural APD dispersion, and amiodarone that decreases it.
Simulations with the 1D virtual ventricular wall show that under d-sotalol
conditions the vulnerable window is substantially wider compared to amiodarone
conditions, primarily in the epicardial region where unidirectional conduction
block persists until the adjacent M cells are fully repolarised. Further
simulations with the 3D ventricular wedge have shown that ectopic stimulation of
the epicardial region results in generation of sustained re-entry under
d-sotalol conditions, but not under amiodarone conditions or in control. Again,
APD increase in M cells was identified as the major contributor to tissue
vulnerability--re-entry was initiated primarily due to ectopic excitation
propagating around the unidirectional conduction block in the M cell region.
This suggests an electrophysiological mechanism for the anti- and proarrhythmic
effects of the class III drugs: the relative safety of amiodarone in comparison
to d-sotalol can be explained by relatively low transmural APD dispersion, and
hence, a narrow vulnerable window and low probability of re-entry in the tissue.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Benson AP, Aslanidi OV, Zhang H, Holden AV. (2008) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230101 | BioModels
Project description:This a model from the article:
The canine virtual ventricular wall: a platform for dissecting pharmacological
effects on propagation and arrhythmogenesis.
Benson AP, Aslanidi OV, Zhang H, Holden AV. Prog Biophys Mol Biol
2008 Jan-Apr;96(1-3):187-208 17915298
,
Abstract:
We have constructed computational models of canine ventricular cells and
tissues, ultimately combining detailed tissue architecture and heterogeneous
transmural electrophysiology. The heterogeneity is introduced by modifying the
Hund-Rudy canine cell model in order to reproduce experimentally reported
electrophysiological properties of endocardial, midmyocardial (M) and epicardial
cells. These models are validated against experimental data for individual ionic
current and action potential characteristics, and their rate dependencies. 1D
and 3D heterogeneous virtual tissues are constructed, with detailed tissue
architecture (anisotropy and orthotropy, due to fibre orientation and sheet
structure) of the left ventricular wall wedge extracted from a diffusion tensor
imaging data set. The models are used to study the effects of tissue
heterogeneity and class III drugs on transmural propagation and tissue
vulnerability to re-entry. We have determined relationships between the
transmural dispersion of action potential duration (APD) and the vulnerable
window in the 1D virtual ventricular wall, and demonstrated how changes in the
transmural heterogeneity, and hence tissue vulnerability, can lead to generation
of re-entry in the 3D ventricular wedge. Two class III drugs with opposite
qualitative effects on transmural APD heterogeneity are considered: d-sotalol
that increases transmural APD dispersion, and amiodarone that decreases it.
Simulations with the 1D virtual ventricular wall show that under d-sotalol
conditions the vulnerable window is substantially wider compared to amiodarone
conditions, primarily in the epicardial region where unidirectional conduction
block persists until the adjacent M cells are fully repolarised. Further
simulations with the 3D ventricular wedge have shown that ectopic stimulation of
the epicardial region results in generation of sustained re-entry under
d-sotalol conditions, but not under amiodarone conditions or in control. Again,
APD increase in M cells was identified as the major contributor to tissue
vulnerability--re-entry was initiated primarily due to ectopic excitation
propagating around the unidirectional conduction block in the M cell region.
This suggests an electrophysiological mechanism for the anti- and proarrhythmic
effects of the class III drugs: the relative safety of amiodarone in comparison
to d-sotalol can be explained by relatively low transmural APD dispersion, and
hence, a narrow vulnerable window and low probability of re-entry in the tissue.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Benson AP, Aslanidi OV, Zhang H, Holden AV. (2008) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230087 | BioModels
Project description:This a model from the article:
The canine virtual ventricular wall: a platform for dissecting pharmacological
effects on propagation and arrhythmogenesis.
Benson AP, Aslanidi OV, Zhang H, Holden AV. Prog Biophys Mol Biol
2008 Jan-Apr;96(1-3):187-208 17915298
,
Abstract:
We have constructed computational models of canine ventricular cells and
tissues, ultimately combining detailed tissue architecture and heterogeneous
transmural electrophysiology. The heterogeneity is introduced by modifying the
Hund-Rudy canine cell model in order to reproduce experimentally reported
electrophysiological properties of endocardial, midmyocardial (M) and epicardial
cells. These models are validated against experimental data for individual ionic
current and action potential characteristics, and their rate dependencies. 1D
and 3D heterogeneous virtual tissues are constructed, with detailed tissue
architecture (anisotropy and orthotropy, due to fibre orientation and sheet
structure) of the left ventricular wall wedge extracted from a diffusion tensor
imaging data set. The models are used to study the effects of tissue
heterogeneity and class III drugs on transmural propagation and tissue
vulnerability to re-entry. We have determined relationships between the
transmural dispersion of action potential duration (APD) and the vulnerable
window in the 1D virtual ventricular wall, and demonstrated how changes in the
transmural heterogeneity, and hence tissue vulnerability, can lead to generation
of re-entry in the 3D ventricular wedge. Two class III drugs with opposite
qualitative effects on transmural APD heterogeneity are considered: d-sotalol
that increases transmural APD dispersion, and amiodarone that decreases it.
Simulations with the 1D virtual ventricular wall show that under d-sotalol
conditions the vulnerable window is substantially wider compared to amiodarone
conditions, primarily in the epicardial region where unidirectional conduction
block persists until the adjacent M cells are fully repolarised. Further
simulations with the 3D ventricular wedge have shown that ectopic stimulation of
the epicardial region results in generation of sustained re-entry under
d-sotalol conditions, but not under amiodarone conditions or in control. Again,
APD increase in M cells was identified as the major contributor to tissue
vulnerability--re-entry was initiated primarily due to ectopic excitation
propagating around the unidirectional conduction block in the M cell region.
This suggests an electrophysiological mechanism for the anti- and proarrhythmic
effects of the class III drugs: the relative safety of amiodarone in comparison
to d-sotalol can be explained by relatively low transmural APD dispersion, and
hence, a narrow vulnerable window and low probability of re-entry in the tissue.
This model was taken from the CellML repository
and automatically converted to SBML.
The original model was:
Benson AP, Aslanidi OV, Zhang H, Holden AV. (2008) - version=1.0
The original CellML model was created by:
Catherine Lloyd
c.lloyd@auckland.ac.nz
The University of Auckland
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not..
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2005-01-01 | MODEL1006230078 | BioModels