Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Bases de datos
Tipo del documento
Intervalo de año de publicación
1.
Mol Ther ; 31(9): 2651-2661, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37394797

RESUMEN

Mutant Z alpha-1 antitrypsin (ATZ) accumulates in globules in the liver and is the prototype of proteotoxic hepatic disease. Therapeutic strategies aiming at clearance of polymeric ATZ are needed. Transient receptor potential mucolipin-1 (TRPML1) is a lysosomal Ca2+ channel that maintains lysosomal homeostasis. In this study, we show that by increasing lysosomal exocytosis, TRPML1 gene transfer or small-molecule-mediated activation of TRPML1 reduces hepatic ATZ globules and fibrosis in PiZ transgenic mice that express the human ATZ. ATZ globule clearance induced by TRPML1 occurred without increase in autophagy or nuclear translocation of TFEB. Our results show that targeting TRPML1 and lysosomal exocytosis is a novel approach for treatment of the liver disease due to ATZ and potentially other diseases due to proteotoxic liver storage.


Asunto(s)
Hepatopatías , Canales de Potencial de Receptor Transitorio , alfa 1-Antitripsina , Animales , Humanos , Ratones , alfa 1-Antitripsina/genética , alfa 1-Antitripsina/metabolismo , Hepatopatías/metabolismo , Lisosomas/metabolismo , Ratones Transgénicos , Canales de Potencial de Receptor Transitorio/genética , Canales de Potencial de Receptor Transitorio/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA