Monitoring of Intracellular Tau Aggregation Regulated by OGA/OGT Inhibitors.
Int J Mol Sci
; 16(9): 20212-24, 2015 Aug 26.
Article
en En
| MEDLINE
| ID: mdl-26343633
ABSTRACT
Abnormal phosphorylation of tau has been considered as a key pathogenic mechanism inducing tau aggregation in multiple neurodegenerative disorders, collectively called tauopathies. Recent evidence showed that tau phosphorylation sites are protected with O-linked ß-N-acetylglucosamine (O-GlcNAc) in normal brain. In pathological condition, tau is de-glycosylated and becomes a substrate for kinases. Despite the importance of O-GlcNAcylation in tau pathology, O-GlcNAc transferase (OGT), and an enzyme catalyzing O-GlcNAc to tau, has not been carefully investigated in the context of tau aggregation. Here, we investigated intracellular tau aggregation regulated by BZX2, an inhibitor of OGT. Upon the inhibition of OGT, tau phosphorylation increased 2.0-fold at Ser199 and 1.5-fold at Ser396, resulting in increased tau aggregation. Moreover, the BZX2 induced tau aggregation was efficiently reduced by the treatment of Thiamet G, an inhibitor of O-GlcNAcase (OGA). Our results demonstrated the protective role of OGT in tau aggregation and also suggest the counter-regulatory mechanism of OGA and OGT in tau pathology.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas tau
/
N-Acetilglucosaminiltransferasas
/
Inhibidores Enzimáticos
/
Agregación Patológica de Proteínas
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2015
Tipo del documento:
Article
País de afiliación:
Corea del Sur