Korean J Physiol Pharmacol.  2011 Apr;15(2):107-114. 10.4196/kjpp.2011.15.2.107.

Suppression of Autophagy and Activation of Glycogen Synthase Kinase 3beta Facilitate the Aggregate Formation of Tau

• Kim SI
• Lee WK
• Kang SS
• Lee SY
• Jeong MJ
• Lee HJ
• Kim SS
• Johnson GV
• Chun W

• KMID: 2285415
• DOI: http://doi.org/10.4196/kjpp.2011.15.2.107

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.

Keyword

Tau; Autopahgy; Glycogen synthase kinase 3beta; Trehalose; Neurofibrillary tangles

MeSH Terms

Adenine
Alzheimer Disease
Autophagy
Glycogen
Glycogen Synthase
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Neurofibrillary Tangles
Phosphorylation
Trehalose
Adenine
Glycogen
Glycogen Synthase
Glycogen Synthase Kinase 3
Glycogen Synthase Kinases
Trehalose

Reference

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