Lysosomal functions of progranulin and implications for treatment of frontotemporal dementia.
Trends Cell Biol
; 33(4): 324-339, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36244875
ABSTRACT
Loss-of-function heterozygous mutations in GRN, the gene encoding progranulin (PGRN), were identified in patients with frontotemporal lobar degeneration (FTLD) almost two decades ago and are generally linked to reduced PGRN protein expression levels. Although initial characterization of PGRN function primarily focused on its role in extracellular signaling as a secreted protein, more recent studies revealed critical roles of PGRN in regulating lysosome function, including proteolysis and lipid degradation, consistent with its lysosomal localization. Emerging from these studies is the notion that PGRN regulates glucocerebrosidase activity via direct chaperone activities and via interaction with prosaposin (i.e., a key regulator of lysosomal sphingolipid-metabolizing enzymes), as well as with the anionic phospholipid bis(monoacylglycero)phosphate. This emerging lysosomal biology of PGRN identified novel and promising opportunities in therapeutic discovery as well as biomarker development.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Degeneração Lobar Frontotemporal
/
Demência Frontotemporal
Limite:
Humans
Idioma:
En
Revista:
Trends Cell Biol
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos