Protective Proteolysis in Huntington's Disease: Unraveling the Role of Post-Translational Myristoylation of Huntingtin in Autophagy.
J Huntingtons Dis
; 13(3): 267-277, 2024.
Article
en En
| MEDLINE
| ID: mdl-38995796
ABSTRACT
Huntington's disease (HD) is a devastating neurodegenerative disorder characterized by impaired motor function and cognitive decline, ultimately leading to death. HD is caused by a polyglutamine expansion in the N-terminal region of the huntingtin (HTT) protein, which is linked to decreased HTT turnover, increased HTT proteolysis, increased HTT aggregation, and subsequent neuronal death. In this review, we explore the mechanism of the protective effect of blocking HTT proteolysis at D586, which has been shown to rescue the HD phenotype in HD mouse models. Until recently, the mechanism remained unclear. Herein, we discuss how blocking HTT proteolysis at D586 promotes HTT turnover by correcting autophagy, and making HTT a better autophagy substrate, through post-translational myristoylation of HTT at G553.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Procesamiento Proteico-Postraduccional
/
Enfermedad de Huntington
/
Proteolisis
/
Proteína Huntingtina
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Huntingtons Dis
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Países Bajos