title: Glycogen synthase kinase-3 regulates production of amyloid-β peptides and tau phosphorylation in diabetic rat brain.
abstract: The pathogenesis of diabetic neurological complications is not fully understood. Diabetes mellitus (DM) and Alzheimer's disease (AD) are characterized by amyloid deposits. Glycogen synthase kinase-3 (GSK-3) plays an important role in the pathogenesis of AD and DM. Here we tried to investigate the production of amyloid-β peptides (A β) and phosphorylation of microtubule-associated protein tau in DM rats and elucidate the role of GSK-3 and Akt (protein kinase B, PKB) in these processes. Streptozotocin injection-induced DM rats displayed an increased GSK-3 activity, decreased activity and expression of Akt. And A β 40 and A β 42 were found overproduced and the microtubule-associated protein tau was hyperphosphorylated in the hippocampus. Furthermore, selective inhibition of GSK-3 by lithium could attenuate the conditions of A β overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of A β and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Zhong-Sen
authors: ZS
authors: Qu
authors: Department of Neurology, The Central Hospital Affiliated Qingdao University, Qingdao 266042, China.
authors: Liang
authors: L
authors: Li
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Xiao-Jiang
authors: XJ
authors: Sun
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Yu-Wu
authors: YW
authors: Zhao
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Jin
authors: J
authors: Zhang
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Zhi
authors: Z
authors: Geng
authors: Department of Neurology, The Sixth People's Hospital Affiliated Shanghai Jiao Tong University, Yi Shan Road 600, Shanghai 200233, China.
authors: Jian-Liang
authors: JL
authors: Fu
authors: Department of Pathophysiology, Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
authors: Qing-Guo
authors: QG
authors: Ren
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D001786:Blood Glucose; D001921:Brain / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000378:metabolism*; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001786:Blood Glucose; D016875:tau Proteins; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3