Multidimensional Dynamics of the Proteome in the Neurodegenerative and Aging Mammalian Brain.

ABSTRACT: The amount of any given protein in the brain is determined by the rates of its synthesis and destruction, which are regulated by different cellular mechanisms. Here, we combine metabolic labeling in live mice with global proteomic profiling to simultaneously quantify both the flux and amount of proteins in mouse models of neurodegeneration. In multiple models, protein turnover increases were associated with increasing pathology. This method distinguishes changes in protein expression mediated by synthesis from those mediated by degradation. In the App^NL-F knockin mouse model of Alzheimer's disease, increased turnover resulted from imbalances in both synthesis and degradation, converging on proteins associated with synaptic vesicle recycling (Dnm1, Cltc, Rims1) and mitochondria (

SUBMITTER: Andrews B 

PROVIDER: S-EPMC8816717 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature