SorLA Protective Function Is Restored by Improving SorLA Protein Maturation in a Subset of Alzheimer's Disease-Associated SORL1 Missense Variants.
J Alzheimers Dis
; 94(4): 1343-1349, 2023.
Article
en En
| MEDLINE
| ID: mdl-37424467
ABSTRACT
SORL1 loss of function is associated with Alzheimer's disease (AD) risk through increased Aß peptide secretion. We expressed 10 maturation-defective rare missense SORL1 variants in HEK cells and showed that decreasing growing temperature led to a significant increase in the maturation of the encoded protein SorLA for 6/10. In edited hiPSC carrying two of these variants, maturation of the protein was restored partially by decreasing the culture temperature and was associated with concomitant decrease in Aß secretion. Correcting SorLA maturation in the context of maturation-defective missense variants could thus be a relevant strategy to improve SorLA protective function against AD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Alzheimers Dis
Asunto de la revista:
GERIATRIA
/
NEUROLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Francia