Suppression of Autophagy and Activation of Glycogen Synthase Kinase 3beta Facilitate the Aggregate Formation of Tau
The Korean Journal of Physiology and Pharmacology
;
: 107-114, 2011.
Article
in English
| WPRIM
| ID: wpr-727370
ABSTRACT
Neurofibrillary tangle (NFT) is a characteristic hallmark of Alzheimer's disease. GSK3beta has been reported to play a major role in the NFT formation of tau. Dysfunction of autophagy might facilitate the aggregate formation of tau. The present study examined the role of GSK3beta-mediated phosphorylation of tau species on their autophagic degradation. We transfected wild type tau (T4), caspase-3-cleaved tau at Asp421 (T4C3), or pseudophosphorylated tau at Ser396/Ser404 (T4-2EC) in the presence of active or enzyme-inactive GSK3beta. Trehalose and 3-methyladenine (3-MA) were used to enhance or inhibit autophagic activity, respectively. All tau species showed increased accumulation with 3-MA treatment whereas reduced with trehalose, indicating that tau undergoes autophagic degradation. However, T4C3 and T4-2EC showed abundant formation of oligomers than T4. Active GSK3beta in the presence of 3-MA resulted in significantly increased formation of insoluble tau aggregates. These results indicate that GSK3beta-mediated phosphorylation and compromised autophagic activity significantly contribute to tau aggregation.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Autophagy
/
Trehalose
/
Adenine
/
Neurofibrillary Tangles
/
Glycogen Synthase
/
Glycogen Synthase Kinases
/
Glycogen Synthase Kinase 3
/
Alzheimer Disease
/
Glycogen
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2011
Type:
Article
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