期刊
NEUROBIOLOGY OF DISEASE
卷 40, 期 2, 页码 449-455出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.07.005
关键词
Alzheimer's disease; Diabetes; Tau phosphorylation; Rosiglitazone; PPAR gamma
资金
- Korean government [R13-2008-023-01001]
Increasing evidence supports an association between Alzheimer's disease (AD) and diabetes. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma (PPAR gamma) agonist, which is an anti-diabetic agent against type 2 diabetes, is currently in Phase Ill clinical trials in AD patients because rosiglitazone reduces beta-amyloid (A beta) pathology and inflammation. However, few studies have investigated whether rosiglitazone affects tau phosphorylation, another critical pathological feature of AD. Thus, we investigated it using OLETF type 2 diabetic rats and streptozotocin-injected type I diabetic mice. Interestingly, rosiglitazone reduced tau phosphorylation only in the hippocampus of OLETF type 2 diabetes rats, and not in that of STZ-injected type 1 diabetes mice. The activity of JNK was reduced in the hippocampus of rosiglitazone-treated OLETF rats, correlating with a reduction in tau phosphorylation, however, which was not correlated with GSK3 beta activity. In human tau-transfected SH-SY5Y neuronal cell line, reduction of tau phosphorylation was also associated with reduction of JNK activity, not of GSK3 beta activity. Hence, rosiglitazone could be used in reducing tau phosphorylation through JNK inactivation for therapeutic effects in type 2 diabetes related Alzheimer's disease. (c) 2010 Elsevier Inc. All rights reserved.
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