Prediction and verification of the AD-FTLD common pathomechanism based on dynamic molecular network analysis.

ABSTRACT: 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.

SUBMITTER: Jin M 

PROVIDER: S-EPMC8361101 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature