TY - JOUR
T1 - Co-expression network analysis of human tau-transgenic mice reveals protein modules associated with tau-induced pathologies
AU - Tsumagari, Kazuya
AU - Sato, Yoshiaki
AU - Shimozawa, Aki
AU - Aoyagi, Hirofumi
AU - Okano, Hideyuki
AU - Kuromitsu, Junro
N1 - Funding Information:
We would like to thank members of Eisai-Keio Innovation Laboratory for Dementia for fruitful discussions. KT is grateful to Koshi Imami ( RIKEN ) for supporting revision work at the current laboratory. This work was supported by a grant from Japan Agency for Medical Research and Development ( JP17pc0101006 ).
Funding Information:
We would like to thank members of Eisai-Keio Innovation Laboratory for Dementia for fruitful discussions. KT is grateful to Koshi Imami (RIKEN) for supporting revision work at the current laboratory. This work was supported by a grant from Japan Agency for Medical Research and Development (JP17pc0101006). KT designed and performed all proteomics experiments, analyzed the data, and wrote the article. AS performed immunofluorescence microscopy experiments. YS, HA, and JK supervised the study. All authors interpreted the data and reviewed the article. YS, HA, and JK are employed by Eisai Co. Ltd.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/8/19
Y1 - 2022/8/19
N2 - Abnormally accumulated tau protein aggregates are one of the hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD). In order to investigate proteomic alteration driven by tau aggregates, we implemented quantitative proteomics to analyze disease model mice expressing human MAPTP301S transgene (hTau-Tg) and quantified more than 9,000 proteins in total. We applied the weighted gene co-expression analysis (WGCNA) algorithm to the datasets and explored protein co-expression modules that were associated with the accumulation of tau aggregates and were preserved in proteomes of AD brains. This led us to identify four modules with functions related to neuroinflammatory responses, mitochondrial energy production processes (including the tricarboxylic acid cycle and oxidative phosphorylation), cholesterol biosynthesis, and postsynaptic density. Furthermore, a phosphoproteomics study uncovered phosphorylation sites that were highly correlated with these modules. Our datasets represent resources for understanding the molecular basis of tau-induced neurodegeneration, including AD.
AB - Abnormally accumulated tau protein aggregates are one of the hallmarks of neurodegenerative diseases, including Alzheimer's disease (AD). In order to investigate proteomic alteration driven by tau aggregates, we implemented quantitative proteomics to analyze disease model mice expressing human MAPTP301S transgene (hTau-Tg) and quantified more than 9,000 proteins in total. We applied the weighted gene co-expression analysis (WGCNA) algorithm to the datasets and explored protein co-expression modules that were associated with the accumulation of tau aggregates and were preserved in proteomes of AD brains. This led us to identify four modules with functions related to neuroinflammatory responses, mitochondrial energy production processes (including the tricarboxylic acid cycle and oxidative phosphorylation), cholesterol biosynthesis, and postsynaptic density. Furthermore, a phosphoproteomics study uncovered phosphorylation sites that were highly correlated with these modules. Our datasets represent resources for understanding the molecular basis of tau-induced neurodegeneration, including AD.
KW - Molecular biology
KW - omics
KW - proteomics
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U2 - 10.1016/j.isci.2022.104832
DO - 10.1016/j.isci.2022.104832
M3 - Article
AN - SCOPUS:85135712524
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 8
M1 - 104832
ER -
