Glycogen Synthase Kinase-3 Regulates Production of Amyloid-β Peptides and Tau Phosphorylation in Diabetic Rat Brain

Autor: Zhong-Sen Qu, Liang Li, Xiao-Jiang Sun, Yu-Wu Zhao, Jin Zhang, Zhi Geng, Jian-Liang Fu, Qing-Guo Ren
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: The Scientific World Journal, Vol 2014 (2014)
Druh dokumentu: article
ISSN: 2356-6140
1537-744X
DOI: 10.1155/2014/878123
Popis: 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 (Aβ) 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 Aβ40 and Aβ42 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 Aβ overproduction and tau hyperphosphorylation. Taken together, our studies suggest that GSK-3 regulates both the production of Aβ and the phosphorylation of tau in rat brain and may therefore contribute to DM caused AD-like neurological defects.
Databáze: Directory of Open Access Journals
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