Multidimensional Dynamics of the Proteome in the Neurodegenerative and Aging Mammalian Brain.
Mol Cell Proteomics
; 21(2): 100192, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34979241
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 AppNL-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 (Fis1, Ndufv1). In contrast to disease models, aging in wild-type mice caused a widespread decrease in protein recycling associated with a decrease in autophagic flux. Overall, this simple multidimensional approach enables a comprehensive mapping of proteome dynamics and identifies affected proteins in mouse models of disease and other live animal test settings.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteoma
/
Enfermedad de Alzheimer
Límite:
Animals
Idioma:
En
Revista:
Mol Cell Proteomics
Asunto de la revista:
BIOLOGIA MOLECULAR
/
BIOQUIMICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Reino Unido