期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 175, 期 5, 页码 2089-2098出版社
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2009.090157
关键词
-
类别
资金
- New York State Office of Mental Retardation and Developmental Disabilities
- U.S. National Institute of Health [R01 AG027429, R01 AG019158]
- U.S. Alzheimer's Association [IIRG-05-13095]
- Education Ministry of China
- Applied Basic Research Program Foundation of Tianjin City, China [08JCYBJC27500]
- Science and Technique Development Projects for Higher Educational Institutions of Tianjin City, China [20070203]
Recent studies have suggested a possible role of insulin dysfunction in the pathogenesis of sporadic Alzheimer's disease (AD). in AD, brain glucose metabolism is impaired, and this impairment appears to precede the pathology and clinical symptoms of the disease. However, the exact contribution of impaired insulin signaling to AD is not known. In this study, by using a nontransgenic rat model of sporadic AD generated by intracerebroventricular administration of streptozotocin, we investigated insulin signaling, glucose transporters, protein O-GlcNAcylation, and phosphorylation of tau and neurofilaments in the brain. We found impaired insulin signaling, overactivation of glycogen synthase kinase-3 beta, decreased levels of major brain glucose transporters, down-regulated protein O-GlcNAcylation, increased phosphorylation of tau and neurofilaments, and decreased microtubule-binding activity of tau in the brains of streptozotocin-treated rats. These results suggest that impaired brain insulin signaling may lead to overactivation of glycogen synthase kinase-3 beta and down-regulation of O-GicNAcylation, which, in turn, facilitate abnormal hyperphosphorylation of tau and neurofilaments and, consequently, neurofibrillary degeneration. (Am j Pathol 2009,175:2089-2098; DOI: 10.2353/ajpath.2009.090157)
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据