دورية أكاديمية
Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis
| العنوان: | Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis |
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| المؤلفون: | Jin, Meihua, Jin, Xiaocen, Homma, Hidenori, Fujita, Kyota, Tanaka, Hikari, Murayama, Shigeo, Akatsu, Hiroyasu, Tagawa, Kazuhiko, Okazawa, Hitoshi |
| المساهمون: | MEXT | Japan Society for the Promotion of Science, Japan Agency for Medical Research and Development |
| المصدر: | Communications Biology ; volume 4, issue 1 ; ISSN 2399-3642 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | General Agricultural and Biological Sciences, General Biochemistry, Genetics and Molecular Biology, Medicine (miscellaneous) |
| الوصف: | 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 (PGRN R504X -KI, TDP43 N267S -KI, VCP T262A -KI and CHMP2B Q165X -KI mice) together with four transgenic mouse models of Alzheimer’s disease (AD) and with APP KM670/671NL -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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s42003-021-02475-6 |
| الإتاحة: | https://doi.org/10.1038/s42003-021-02475-6Test https://www.nature.com/articles/s42003-021-02475-6.pdfTest https://www.nature.com/articles/s42003-021-02475-6Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.F182E24A |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s42003-021-02475-6 |
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