ATase inhibition rescues age-associated proteotoxicity of the secretory pathway.
Commun Biol
; 5(1): 173, 2022 02 25.
Article
en En
| MEDLINE
| ID: mdl-35217767
ABSTRACT
Malfunction of autophagy contributes to the progression of many chronic age-associated diseases. As such, improving normal proteostatic mechanisms is an active target for biomedical research and a key focal area for aging research. Endoplasmic reticulum (ER)-based acetylation has emerged as a mechanism that ensures proteostasis within the ER by regulating the induction of ER specific autophagy. ER acetylation is ensured by two ER-membrane bound acetyltransferases, ATase1 and ATase2. Here, we show that ATase inhibitors can rescue ongoing disease manifestations associated with the segmental progeria-like phenotype of AT-1 sTg mice. We also describe a pipeline to reliably identify ATase inhibitors with promising druggability properties. Finally, we show that successful ATase inhibitors can rescue the proteopathy of a mouse model of Alzheimer's disease. In conclusion, our study proposes that ATase-targeting approaches might offer a translational pathway for many age-associated proteopathies affecting the ER/secretory pathway.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Retículo Endoplásmico
/
Vías Secretoras
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Año:
2022
Tipo del documento:
Article