2021年8月12日
Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis.
Communications biology
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- 巻
- 4
- 号
- 1
- 開始ページ
- 961
- 終了ページ
- 961
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1038/s42003-021-02475-6
Multiple gene mutations cause familial frontotemporal lobar degeneration (FTLD) while no single gene mutations exists in sporadic FTLD. Various proteins aggregate in variable regions of the brain, leading to multiple pathological and clinical prototypes. The heterogeneity of FTLD could be one of the reasons preventing development of disease-modifying therapy. We newly develop a mathematical method to analyze chronological changes of PPI networks with sequential big data from comprehensive phosphoproteome of four FTLD knock-in (KI) mouse models (PGRNR504X-KI, TDP43N267S-KI, VCPT262A-KI and CHMP2BQ165X-KI mice) together with four transgenic mouse models of Alzheimer's disease (AD) and with APPKM670/671NL-KI mice at multiple time points. The new method reveals the common core pathological network across FTLD and AD, which is shared by mouse models and human postmortem brains. Based on the prediction, we performed therapeutic intervention of the FTLD models, and confirmed amelioration of pathologies and symptoms of four FTLD mouse models by interruption of the core molecule HMGB1, verifying the new mathematical method to predict dynamic molecular networks.
- リンク情報
- ID情報
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- DOI : 10.1038/s42003-021-02475-6
- PubMed ID : 34385591
- PubMed Central 記事ID : PMC8361101